Aortic blood flow meter and pump for partial aortic occlusion

Abstract

Systems and methods for partial aortic occlusion are provided. The system may include a catheter positioned within a patient's aorta, the catheter having an expandable aortic blood flow regulation device located at a distal end of the catheter, and a catheter control device that expands and contracts the device to restrict aortic blood flow. The system may also include sensors for measuring blood pressure distal and proximal to the expandable device. The system may further include a non-transitory computer-readable medium storing instructions that, when executed by a processor coupled to the sensor, cause the processor to estimate aortic blood flow based on the blood pressure measurements and corresponding waveforms, compare the estimated aortic blood flow with a target aortic blood flow range, generate an alarm if the estimated aortic blood flow is outside the target aortic blood flow range, and cause the catheter control device to adjust the expansion and contraction of the expandable device to regulate aortic blood flow if the estimated aortic blood flow is outside the target aortic blood flow range.

Description

[Technical field]

[0001] Statement of Government Interest This invention was made with Government support under Contract No. K12HL108964 awarded by the National Heart, Lung and Blood Institute. The Government has certain rights in this invention.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 62 / 488,625, filed April 21, 2017, the entire contents of which are incorporated herein by reference.

[0003] Fields of use The present disclosure relates generally to an intravascular aortic blood flow regulation device for placement within the aorta. More specifically, the present invention relates to a precision control system and method for achieving partial occlusion of the aorta. [Background technology]

[0004] background Hemorrhage is a leading cause of preventable death in civilians and military personnel and is particularly difficult to control when it occurs due to non-compressive vascular injury. In the vast majority of cases in both medical and surgical patients, there continues to be a high rate of death due to hemorrhagic complications from trauma and shock. In many cases, existing systems, drugs, and procedures used to treat shock conditions ultimately result in the death of the patient due to an inability to maintain sufficient oxygen delivery to vital organs. This oxygen delivery is based on sufficient blood perfusion to the organs. It is well recognized that insufficient cardiac and pulmonary blood pressure leads to hemodynamic collapse, which reduces perfusion to remaining organs and ultimately leads to death.

[0005] Resuscitation of patients with shock, whether neurogenic, hemorrhagic, hypovolemic, or septic, is a unique challenge in the first hours of critical care. Any hypotensive episode can be harmful to the patient. Elderly patients and those with brain trauma are particularly susceptible to hypotensive episodes. Current practice for treating shock is based on etiology, but nearly all treatment algorithms include IV fluids or blood products and, if necessary, drugs that act on the vasculature to cause vasoconstriction and blood pressure elevation. In situations where bleeding is ongoing, surgical hemorrhage control is often required to stop the bleeding.

[0006] Although the nuances of shock treatment depend on the etiology, all treatment modalities have drawbacks. First, in the setting of hemorrhage, it is often not possible to stop the bleeding before the patient loses blood and dies from hypovolemia.

[0007] Second, in almost all forms of shock, large amounts of IV fluids and / or blood products are often required early in treatment to improve blood pressure. Sometimes, giving too much fluid to the cardiovascular system can lead to pulmonary edema, ARDS, or heart failure. Therefore, alternative methods to remove this excess fluid, often necessary early in treatment, but as soon as the patient can tolerate the diuretic effect, are often needed.

[0008] A third complication of current treatments is a secondary consequence of high doses of vasopressors. Vasopressors act directly on blood vessels to increase vascular tone and improve systemic blood pressure. In the absence of better treatment solutions, these drugs may be necessary to improve perfusion to vital organs. However, this increase in systemic blood pressure comes at the potential cost of poor perfusion at the microvascular level. Unfortunately, differences in responsiveness between organs and tissue beds to these drugs can lead to unpredictable changes in local blood flow that can ultimately have adverse or deleterious effects. High doses of these drugs can cause permanent damage to certain tissues, for example in distal limbs potentially requiring major amputation or in the kidneys, causing renal damage and requiring dialysis. In patients suffering from brain trauma with elevated intracranial pressure, animal and human studies have shown that high doses of vasopressors can often improve perfusion to the damaged area of ​​the brain, often at the expense of other areas of the brain exhibiting significant vasoconstriction resulting in ischemic neuronal damage.

[0009] Finally, current therapies for treating shock take time to work. Massive infusions of blood products and IV fluid boluses take minutes to an hour, and vasopressors often take 10 to 15 minutes to begin to work, often necessitating dose titration over the following hours. Even when they do work, some forms of shock do not respond to a single drug, and multiple vasopressors are required to optimize blood pressure. These conventional therapies are often unable to optimize blood pressure in a timely manner and often fail to achieve their entire intended goal. Because even brief periods of ischemia can result in organ dysfunction and reduced survival, improved strategies are needed to more timely and reliably optimize blood flow and blood pressure.

[0010] The ability to rapidly deliver effective blood pressure and flow to a shocked heart, lungs, and brain immediately prior to the delivery of blood products, crystalloids, and / or blood pressure medications that require more time to function would save countless lives.

[0011] The concept of using a device within the aorta to augment blood pressure is not unique. Resuscitative endovascular balloon blockade of the aorta (REBOA) is a treatment used in terminally ill trauma patients. REBOA emerged as a treatment to provide temporary hemodynamic support and bleeding control via balloon catheters prior to definitive surgical intervention to stop bleeding. Rather than performing an emergency department thoracotomy to cross-clamp the aorta and minimize distal aortic blood flow, a balloon catheter is fully inflated within the aorta beyond the level of injury to stop blood flow. This technology works to completely block the aorta, rapidly improving blood pressure upstream of the catheter if adequate circulation is present.

[0012] Currently, REBOA is a well-established clinical strategy in the management of non-compressible truncal hemorrhage, providing hemodynamic support and minimizing bleeding. Its growing adoption within the trauma community has been driven by the confluence of innovative endovascular and endovascular technologies with strong support from opinion leaders within the vascular and trauma surgery fields. Despite the growing enthusiasm, it is important to recognize that REBOA creates a second physiological insult in patients who are already physiologically compromised. Specifically, the utility of REBOA is limited in terms of its duration of use due to several adverse physiological effects on the upstream and downstream vascular beds. For example, downstream of the balloon, progressive ischemia of tissue beds distal to the blockage point, e.g., organ damage due to lack of blood flow, may occur, and upstream of the balloon, after a prolonged period of time, cardiac, pulmonary, and brain damage may occur due to supraphysiological blood pressures and increased afterload proximal to the balloon. Distal ischemia occurring in tissues below the blockage level limits the REBOA treatment period to 30 to 45 minutes. These side effects are greatest during Zone 1 blockade, which severely limits the total treatment duration of REBOA and therefore the number of patients who can potentially benefit from this therapy, as REBOA can only be performed in settings where a surgeon is available to obtain rapid bleeding control.

[0013] It is not surprising, therefore, that the expanded use of this technology will expose the deleterious consequences of sustained complete aortic cross-clamping. Thus, concerns regarding progressive ischemic burden and potential cardiac dysfunction with complete aortic cross-clamping raise the already high threshold for use of this therapy, especially in scenarios requiring prolonged cross-clamping. This hesitation on the part of healthcare providers is amplified by the fact that the tolerance threshold for REBOA, above which survival is not possible, has not been well defined. This concern inherently narrows the scope of REBOA, reducing its utility in austere or rural settings and interfacility transport.

[0014] A modification of the traditional REBOA technique utilizes partial occlusion of the aorta with a balloon catheter to achieve low distal blood flow rather than completely halting all blood flow as a way to extend the duration of treatment. This technique has been referred to by various names, including but not limited to, resuscitative endovascular balloon partial occlusion of the aorta (PREBOA), and is a viable strategy to mitigate the effects of sustained aortic occlusion. Partial aortic occlusion can extend the duration of treatment by reducing damage below the balloon through the maintenance of blood flow, allowing more time for surgical control of bleeding.

[0015] However, early animal studies have shown that the inability to tightly regulate downstream aortic blood flow to the injured area during REBOA or P-REBOA can result in early mortality due to blood loss. Until now, clinical efficacy of P-REBOA has been difficult to achieve because control of balloon inflation and deflation can only be achieved by manual, low-fidelity manipulation of an inflation syringe. Current balloon technologies created for complete or partial aortic blockage to stop distal bleeding in traumatic situations are unable to achieve consistent titrated blood flow over the full range from complete blockage to no blockage with manual control alone, especially when the intent is to maintain consistent distal blood flow within a narrowly defined range. PryTime Medical's ER-REBOA catheter is a compliant balloon catheter intended to reduce bleeding after trauma and is one type of balloon that may lend itself to precise physician-assisted control using an external syringe pump device.

[0016] As described in Timothy K. Williams, MD, et al., Automated Variable Aortic Control Versus Complete Aortic Occlusion in a Swine Model of Hemorrhage (February 10, 2017) (unpublished) (on file in the Journal of Trauma Acute Care Surgery), the entire contents of which are incorporated herein by reference, partial aortic occlusion can lead to hemodynamic instability and continued bleeding due to poor control of distal aortic blood flow, which limits its usefulness, especially in resource-constrained settings. Thus, current systems are unable to estimate aortic blood flow distal to an expandable partial aortic occlusion device, e.g., a balloon catheter. Currently, practitioners use blood pressure proximal to the occlusion device as a surrogate marker of when partial aortic occlusion is permissible in trauma. As described in M. Austin Johnson, MD, PhD, et al., Small Changes, Big Effects: The Hemodynamics of Partial and Complete Aortic Occlusion to Inform Next Generation Resuscitation Techniques and Technologies (January 5, 2017) (Journal of Trauma and Acute Care Surgery) (on file at Journal of Trauma Acute Care Surgery), the entire contents of which are incorporated herein by reference, proximal blood pressure does not correlate with aortic blood flow across various hemorrhage levels. Thus, the use of proximal blood pressure as a surrogate marker can be harmful, as proximal blood pressure is a poor marker of aortic blood flow, and small changes in the volume of the occlusion device can cause large changes in blood flow, which in turn can cause continued hemorrhage and decompensation.Specifically, the delayed response of proximal blood pressure to these changes in blood flow makes proximal blood pressure a poor surrogate for use in attempting partial aortic cross-clamping. The inability to control low blood flow during uncontrolled bleeding can result in blood loss and death. Furthermore, the inability to detect blood flow can lead to unrecognized complete aortic cross-clamping resulting in progressive ischemia. Thus, clinical application of partial aortic cross-clamping without a means to estimate aortic blood flow beyond the cross-clamping device can be dangerous and result in death.

[0017] In light of the above problems and limitations with existing and proposed devices, there exists an urgent and unmet need for a viable solution that can provide physicians with a means of measuring aortic blood flow and a device that assists in controlling catheter balloon volume to achieve titrated distal blood flow. [Prior art documents] [Non-patent literature]

[0018] [Non-Patent Document 1] Timothy K. Williams, MD, et al., Automated Variable Aortic Control Versus Complete Aortic Occlusion in a Swine Model of Hemorrhage (February 10, 2017) (unpublished) (on file in the Journal of Trauma Acute Care Surgery) [Non-Patent Document 2] M. Austin Johnson, MD, PhD, et al., Small Changes, Big Effects: The Hemodynamics of Partial and Complete Aortic Occlusion to Inform Next Generation Resuscitation Techniques and Technologies (January 5, 2017) (Journal of Trauma and Acute Care Surgery) Summary of the Invention

[0019] overview The present disclosure overcomes the shortcomings of current intravascular isolation systems by including a series of sensors that measure the patient's physiological condition upstream and downstream from and within the isolation balloon, thereby providing a means to measure aortic blood flow past the isolation balloon.

[0020] The system may include a catheter control device for automating the expansion and contraction of the expandable aortic flow control device, and a balloon positioned within the aorta to partially restrict blood flow through the aorta. The catheter control device may include a pump (e.g., a syringe pump) in fluid communication with the expandable aortic flow control device via the catheter, which may expand and contract the expandable aortic flow control device within the aorta. For example, the pump may inflate or deflate the balloon by delivering a bolus volume as small as one microliter, for example, via a stepper motor.

[0021] The catheter control device may also include a non-transitory computer-readable medium having stored thereon instructions that, when executed by a processor operatively connected to a first sensor positioned distal to the expandable aortic blood flow control device and a second sensor positioned proximal to the expandable aortic blood flow control device, cause the processor to receive information from the first sensor indicative of a blood pressure measurement distal to the expandable aortic blood flow control device, receive information from the second sensor indicative of a blood pressure measurement proximal to the expandable aortic blood flow control device, estimate an aortic blood flow (e.g., an aortic blood flow distal to the expandable aortic blood flow control device) based on the information from the first sensor and the information from the second sensor, compare the estimated aortic blood flow to a target aortic blood flow range, and cause the pump to adjust expansion and contraction of the expandable aortic blood flow control device to adjust the aortic blood flow if the estimated aortic blood flow is outside the target aortic blood flow range.

[0022] In one aspect, the processor causes the catheter control device to automatically adjust the expansion and contraction of the expandable aortic blood flow regulation device to adjust the aortic blood flow when the estimated aortic blood flow is outside of a target aortic blood flow range based on the comparison. In another aspect, the processor causes the catheter control device to adjust the expansion and contraction of the expandable aortic blood flow regulation device to adjust the aortic blood flow when the estimated aortic blood flow is outside of a target aortic blood flow range in response to user input received via a plurality of switches and / or buttons operatively connected to the catheter control device. For example, the system can include a graphical user interface capable of displaying information indicative of the comparison, and further, the graphical user interface can communicate, e.g., visually or audibly, decision support based on the comparison so that a user can provide user input based on the decision support. The processor can also issue an alert when the estimated aortic blood flow is outside of a target aortic blood flow range.

[0023] The system may further include an expandable aortic blood flow regulator located at a distal end of the catheter for placement within the aorta. The expandable aortic blood flow regulator may expand to restrict and constrict blood flow in the aorta. The system may further include one or more sensors for measuring physiological information indicative of blood flow in the aorta. For example, a distal sensor may be located on the catheter distal to the expandable aortic blood flow regulator and may measure physiological information, such as blood pressure, of the aorta distal to the expandable aortic blood flow regulator, and a proximal sensor may be located on the catheter proximal to the expandable aortic blood flow regulator and may measure physiological information, such as blood pressure, of the aorta proximal to the expandable aortic blood flow regulator. The one or more sensors may also measure physiological information indicative of blood flow in the aorta, including at least one of pressure within the expandable aortic blood flow regulator, heart rate, respiratory rate, blood temperature, cardiac output of the patient, carotid blood flow, pulmonary artery pressure, peripheral vascular resistance, or intracranial pressure. In embodiments in which two expandable aortic blood flow control devices are utilized, a distal sensor can be positioned distal to the expandable aortic blood flow control device, a proximal sensor can be positioned proximal to a second expandable aortic blood flow control device, and an additional sensor can be positioned between the expandable aortic blood flow control device and the second expandable aortic blood flow control device.

[0024] In one embodiment, the system may further include one or more sensors, such as a distal sensor and a proximal sensor, a sensor of balloon catheter pressure, and an external central processing unit operatively connected to the catheter control device. The external central processing unit may include a processor and may communicate information to the catheter control device indicating whether the estimated aortic blood flow is outside of a target aortic blood flow range. For example, the external central processing unit may communicate information to the catheter control device via at least one of WiFi, Bluetooth, Wixel-based communication, cellular communication, or other forms of communication.

[0025] According to yet another aspect of the present disclosure, a method is provided for dynamically adjusting the degree of aortic blood flow regulation for partial REBOA, partial aortic occlusion, or augmented endovascular perfusion. The method may include introducing a distal end of a catheter having an expandable aortic blood flow regulation device (e.g., a balloon) into a patient's aorta; expanding the expandable aortic blood flow regulation device with a catheter control device (e.g., a syringe pump) coupled to an outer end of the catheter to partially block blood flow in the aorta; measuring blood pressure distal to the expandable aortic blood flow regulation device and blood pressure proximal to the expandable aortic blood flow regulation device with one or more sensors, a sensor measuring pressure in the balloon catheter; estimating aortic blood flow based on waveforms of the blood pressure measurements distal and proximal to the expandable aortic blood flow regulation device and corresponding waveforms of the blood pressure measurements; comparing the estimated aortic blood flow to a target aortic blood flow range; issuing an alarm if the estimated aortic blood flow is outside the target aortic blood flow range; and adjusting expansion and contraction of the expandable aortic blood flow regulation device to adjust blood flow in the aorta if the estimated aortic blood flow is outside the target aortic blood flow range. The method may also include measuring pressure within the expandable aortic flow regulator device.The method may further include displaying information indicative of the comparison via a graphical user interface coupled to the one or more sensors.

[0026] In one embodiment, adjusting the expansion and contraction of the expandable aortic blood flow regulation device to regulate aortic blood flow when the estimated aortic blood flow is outside of the target aortic blood flow range is performed automatically, while in another embodiment, adjusting the expansion and contraction of the expandable aortic blood flow regulation device to regulate aortic blood flow when the estimated aortic blood flow is outside of the target aortic blood flow range is performed in response to user input received via a plurality of switches and / or buttons operatively connected to the catheter control device. [The present invention 1001] A catheter control device for automating the expansion and contraction of an expandable blood flow control device that is placed in a blood vessel to partially restrict blood flow through the blood vessel, the expandable blood flow control device being placed in a distal end region of a catheter, the catheter control device comprising: a pump in fluid communication with the expandable flow control device via the catheter, the pump configured to expand and contract the expandable flow control device within the blood vessel; A non-transitory computer readable medium storing instructions, which when executed by a processor operatively connected to a first sensor positioned distal to the expandable blood flow regulator and a second sensor positioned proximal to the expandable blood flow regulator, the instructions causing the processor to: receiving information from the first sensor indicative of a blood pressure measurement value or a waveform of the blood pressure measurement value distal to the expansive blood flow regulator; receiving information from the second sensor indicative of a blood pressure measurement or a waveform of the blood pressure measurement proximal to the expandable flow regulator; estimating vascular blood flow based on the information from the first sensor and the information from the second sensor; Comparing the estimated blood flow to a target blood flow range; and causing the pump to adjust expansion and contraction of the expandable blood flow control device to regulate blood flow in the blood vessel when the estimated blood flow is outside the target blood flow range. A non-transitory computer-readable medium; A catheter control device comprising: [The present invention 1002] A catheter control device of the present invention 1001, wherein the expandable blood flow regulating device includes a balloon configured to expand to restrict blood flow in a blood vessel, and the pump is configured to expand or contract the balloon to adjust the blood flow in the blood vessel when the estimated blood flow is outside the target blood flow range. [The present invention 1003] The catheter control device of the present invention 1002, wherein the pump is configured to inflate or deflate the balloon by delivering a bolus volume as small as 1 microliter. [The present invention 1004] The catheter control device of the present invention 1002, wherein the pump is configured to inflate or deflate the balloon by a stepper motor connected to the processor. [The present invention 1005] The catheter control device of the present invention 1001, wherein the estimated blood flow rate is the blood flow rate distal to the expandable blood flow control device in the blood vessel. [The present invention 1006] The catheter control device of the present invention 1001, wherein the processor automatically causes the pump to adjust the expansion and contraction of the expandable blood flow regulating device to adjust the blood flow in the blood vessel if the estimated blood flow is outside the target blood flow range based on the comparison. [The present invention 1007] The catheter control device of the present invention 1001 further includes a plurality of switches and / or buttons operatively connected to the processor, and in response to user input received via the plurality of switches and / or buttons, the processor causes the pump to adjust the expansion and contraction of the expandable blood flow regulating device to adjust the blood flow in the blood vessel when the estimated blood flow is outside the target blood flow range. [The present invention 1008] The catheter control device of the present invention 1001 further includes a graphical user interface configured to display information indicative of the comparison, the graphical user interface being further configured to convey decision support based on the comparison, thereby allowing a user to provide user input based on the decision support. [The present invention 1009] The catheter control device of the present invention 1008, wherein the graphical user interface is configured to audibly communicate the decision support. [The present invention 1010] The catheter control device of the present invention 1001, wherein the processor issues an alarm if the estimated blood flow is outside the target blood flow range. [The present invention 1011] A precision control system for partial occlusion of an aorta, comprising the catheter control device of the present invention 1001, an expandable blood flow control device disposed on a distal end of the catheter for placement within a blood vessel, the expandable blood flow control device being configured to expand and contract to restrict blood flow in the blood vessel; a first sensor positioned distal to the expansile blood flow regulator and configured to measure blood pressure distal to the expansile blood flow regulator; and a second sensor positioned proximal to the expandable blood flow regulator and configured to measure blood pressure proximal to the expandable blood flow regulator; The system further comprises: [The present invention 1012] The system of the present invention 1011 further includes one or more sensors configured to measure physiological information indicative of blood flow, including at least one of pressure within the expandable blood flow regulating device, heart rate, respiratory rate, blood temperature, the patient's cardiac output, carotid blood flow, pulmonary artery pressure, peripheral vascular resistance, or intracranial pressure. [The present invention 1013] The system of the present invention 1011, wherein the system further includes an external central processing unit operatively connected to the catheter control device and the first and second sensors, the external central processing unit including a processor and configured to communicate information to the catheter control device indicating whether the estimated blood flow is outside a target blood flow range. [The present invention 1014] The system of the present invention 1013, wherein the external central processing unit communicates the information to the catheter control device via at least one of WiFi, Bluetooth, Wixel-based communication, cellular communication, or other forms of communication. [The present invention 1015] 1. A method for dynamically adjusting a degree of blood flow regulation, comprising: introducing a distal end of a catheter including an expandable flow control device into a patient's blood vessel; expanding the expandable flow control device with a catheter control device coupled to a proximal end of the catheter to restrict blood flow in the blood vessel; measuring blood pressure distal to the expansile blood flow control device and blood pressure proximal to the expansile blood flow control device with one or more sensors; estimating blood flow based on the blood pressure measurements distal and proximal to the expansible flow regulator and corresponding waveforms of the blood pressure measurements; comparing the estimated blood flow to a target blood flow range; issuing an alert if the estimated blood flow is outside the target blood flow range; and adjusting the expansion and contraction of the expandable blood flow control device to regulate blood flow in the blood vessel if the estimated blood flow is outside the target blood flow range. A method comprising: [The present invention 1016] The method of claim 1015, wherein the expandable blood flow control device comprises a balloon configured to expand to restrict blood flow in the blood vessel, and the step of expanding or contracting the expandable blood flow control device comprises inflating or contracting the balloon with a pump. [The present invention 1017] The method of the present invention 1015, wherein the step of adjusting the expansion and contraction of the expandable blood flow control device to adjust the blood flow in the blood vessel when the estimated blood flow is outside the target blood flow range is performed automatically. [The present invention 1018] The method of the present invention 1015, wherein the step of adjusting the expansion and contraction of the expandable blood flow control device to adjust blood flow in the blood vessel when the estimated blood flow is outside the target blood flow range is performed in response to user input received via a plurality of switches and / or buttons operatively connected to the catheter control device. [The present invention 1019] The method of claim 1015, further comprising the step of measuring pressure within the expandable blood flow regulating device. [The present invention 1020] The method of claim 1015 further comprising displaying information indicative of said comparison via a graphical user interface coupled to said one or more sensors. [Brief description of the drawings]

[0027] [Figure 1] FIG. 1 is a schematic diagram of an exemplary precision control system for partial aortic occlusion constructed in accordance with the principles of the present disclosure. [Diagram 2] 1 shows an exemplary balloon catheter constructed in accordance with the principles of the present disclosure. [Diagram 3] 2 illustrates the exemplary sensor of FIG. 1. [Figure 4] FIG. 2 is a schematic diagram of the exemplary catheter control device of FIG. 1. [Diagram 5] FIG. 2 is a schematic diagram of an exemplary external central processing unit constructed in accordance with the principles of the present disclosure. [Figure 6] 1 is a flow chart illustrating an exemplary method for dynamically adjusting the degree of aortic blood flow regulation in accordance with the principles of the present disclosure. [Figure 7] 7A-7C are graphs illustrating the change in mean proximal arterial pressure, mean distal arterial pressure, and aortic blood flow, respectively, in a study according to the principles of the present disclosure. [Figure 8] 8A-8C show the relationship between balloon volume and various hemodynamic parameters in a test according to the principles of the present disclosure, and FIG 8D shows the relationship between aortic blood flow and target aortic blood flow in a test. [Figure 9] FIG. 9A shows the relationship between balloon volume during EVAC and aortic blood flow, and FIG. 9B shows the relationship between balloon volume during EVAC and mean proximal arterial pressure. [Figure 10] 1 is a flow diagram illustrating a test according to the principles of the present disclosure. [Figure 11] 11A-11C are graphs comparing mean proximal arterial pressure, mean distal arterial pressure, and aortic blood flow during REBOA and EVAC studies, respectively. [Figure 12] 12A and 12B show the total amount of resuscitation fluid and vasopressor required during REBOA and EVAC, respectively. [Figure 13] Peak and final lactate levels in REBOA and EVAC are shown. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0028] Detailed Description Resuscitative endovascular balloon partial occlusion of the aorta (P-REBOA) is a partial aortic occlusion platform to reduce distal ischemia and reperfusion injury and alleviate high proximal blood pressure by allowing a controlled, titrated, low amount of aortic blood flow distal to the occlusion site. P-REBOA can be achieved and maintained using techniques described in M. Austin Johnson, MD, PhD, et al., Partial Resuscitative Balloon Occlusion of the Aorta (P-REBOA): Clinical Technique and Rationale, 80 J Trauma Acute Care Surg S133 (2016), the entire contents of which are incorporated herein by reference. Another form of partial aortic occlusion that can be used to improve blood pressure upstream of the balloon during various shock conditions is Enhanced Endovascular Perfusion for Critical Care (EPACC), which is achieved by a system that includes a series of endovascular devices, a controller for the devices, and an algorithm that can change the EPACC devices in real time depending on the patient's physiological state. The EPACC concept works by partial aortic blockage similar to P-REBOA, in contrast to techniques such as REBOA. REBOA completely blocks the aorta, maximizing proximal perfusion at the expense of progressive ischemic injury to distal tissues. In contrast, EPACC only partially blocks the aorta, which allows for a more physiological increase in proximal blood pressure. By placing the balloon at different levels within the aorta, the practitioner can choose which distal capillary beds to reduce blood flow in. Placing the EPACC at the descending thoracic aorta results in a more gradual reduction in blood flow to the mesentery, kidneys, liver, and extremities. In contrast, placement at the aortic bifurcation potentially reduces blood flow only to the pelvis and extremities. Minimal to moderate aortic flow restriction minimizes ischemia, as aortic blood flow often exceeds physiological requirements. This tradeoff between proximal blood pressure increase and distal ischemia varies depending on the degree of shock and the patient's underlying physiologic state.

[0029] The ability to automate partial REBOA, partial aortic blockage, and / or EPACC to dynamically respond to any physiological measurement makes EPACC a viable technique for maximizing perfusion in multiple shock conditions. Endovascular Variable Aortic Control (EVAC) utilizes automated control of aortic blockage to precisely and dynamically regulate distal aortic blood flow over the full range from complete blockage to completely unimpeded blood flow. In surgically specific applications, EVAC technology can be used to restrict distal aortic blood flow to very low levels to strike a delicate balance between continued hemorrhage and progressive distal ischemia while simultaneously augmenting proximal hemodynamics, e.g., increasing blood flow to the heart, lungs, and brain, referred to as Regional Perfusion Optimization (REPO) (formerly known as Permissive Regional Hypoperfusion). REPO is based on a precise and dynamically controllable method of blood flow to the abdominal aorta. For REPO to be clinically applicable, it must be achieved by a precisely controllable endovascular device. In another aspect, these techniques can maximize perfusion in multiple shock conditions by generating decision support that directs the user and / or device to dynamically respond to any physiological measurement.

[0030] REPO with EVAC has been shown to extend the aortic intervention period to 90 minutes with improved survival, end-organ function, and low resuscitation requirements compared to complete aortic clamping, e.g., REBOA, in a porcine model of lethal liver injury. These techniques are equally viable for treating moribund conditions due to blood loss while attempting to obtain surgical control of continued bleeding, for treating septic shock with reduced amounts of IV fluids and vasopressors required for treatment, or for treating neurogenic shock in the setting of brain trauma or intracerebral hemorrhage. As will be appreciated by those skilled in the art, the exemplary catheter control device described herein can be used with any commercially available P-REBOA catheter system or custom-designed catheter system.

[0031] An exemplary precision control system for partial aortic occlusion constructed in accordance with the principles of the present disclosure is described with reference to Figure 1. In Figure 1, the components of precision control system 100 are not shown to scale, either relative or absolute. System 100 includes a catheter control device 400, which is operatively connected to an expandable flow regulator 200 and a sensor 300, and optionally an external processing device.

[0032] The catheter control device 400 can receive data indicative of a physiological information measurement from the sensor 300 and determine whether the physiological information measurement is within a predetermined target physiological range. For example, the catheter control device 400 can receive data indicative of a blood pressure measurement distal to the expandable blood flow regulator and a blood pressure measurement proximal to the expandable blood flow regulator, estimate blood flow based on the blood pressure measurements distal to and proximal to the expandable blood flow regulator and / or waveforms corresponding to the distal and proximal blood pressure measurements, and determine whether the estimated aortic blood flow is within a predetermined target aortic blood flow range.

[0033] The catheter control device 400 can be connected to the expandable blood flow regulator 200 by a catheter sized and shaped to be placed within the aorta A of a patient P. For example, the catheter control device 400 can be connected to the proximal end of a catheter and the expandable blood flow regulator 200 can be located at the distal end of the catheter. The catheter can be any catheter known in the art and has a length sufficient to allow the catheter to be inserted into the patient through the femoral or radial artery and extend through the patient's vasculature into the aorta.

[0034] After placement of a compliant aortic clamping balloon (e.g., blood flow regulation device 200) within the aorta, the catheter can be connected to a catheter control device 400, which can be inflated or deflated to regulate aortic blood flow using manual control of the control device 400 or through decision support that recommends inflation or deflation to the healthcare provider. The expandable blood flow regulation device 200 can be any currently available balloon catheter that is not designed for aortic clamping and may undergo morphological changes over time.

[0035] Also, as described in more detail below, the catheter control device 400 can be coupled to the expandable blood flow regulation device 200 such that the catheter control device 400 automatically adjusts the expansion and contraction of the expandable blood flow regulation device 200 to regulate the aortic blood flow when the physiological information measurements are outside of the target physiological range. In another embodiment, the catheter control device 400 can be coupled to the expandable blood flow regulation device 200 such that in response to user input received by the catheter control device 400, for example, via switches and / or buttons operatively connected to the catheter control device 400, the catheter control device 400 automatically adjusts the expansion and contraction of the expandable blood flow regulation device 200 to regulate the aortic blood flow when the physiological information measurements are outside of the target physiological range. For example, the catheter control device 400 can generate decision support when the physiological information measurements are outside of a predetermined target physiological range, which guides the user to provide sufficient user input to regulate the aortic blood flow such that the patient's physiological condition is within the target physiological range. The catheter control device 400 can expand and contract, for example, in increments of 1 to 50 microliters, the expansion type blood flow regulator 200. The catheter control device 400 can be battery powered or can be directly plugged into an electrical outlet.

[0036] In one embodiment, system 100 may include an external central processing unit operatively connected to sensor 300 and catheter control unit 400 such that the external central processing unit can receive data indicative of the physiological information measurement from sensor 300, determine whether the physiological information measurement is within a predetermined target physiological range, calculate an amount of change in size of expandable flow regulator 200 to bring the patient's physiological condition within the target physiological range, and communicate information indicative of whether the physiological information measurement is outside the target physiological range to catheter control unit 400, as described in more detail below. Thus, catheter control unit 400 automatically adjusts the expansion and contraction of expandable flow regulator 200 based on information received from the external central processing unit to regulate aortic blood flow. In another aspect, the catheter control device 400 adjusts the aortic blood flow by adjusting the expansion and contraction of the expandable flow regulator model 200 when the physiological information measurements are outside of target physiological ranges in response to user input received by the catheter control device 400, where the user input is entered by a user guided by instructions generated by the catheter control device 400 based on information received from an external central processor.

[0037] Referring to FIG. 2, the expandable blood flow regulator 200 of FIG. 1 may be a balloon catheter. Thus, the expandable blood flow regulator 200 may include a balloon 204 located at the tip of the catheter. The balloon 204 is designed to regulate the aortic blood flow by inflating to a carefully titrated balloon volume. For example, a non-compressible fluid may be introduced into the balloon 204 through the lumen of the catheter via the outlet 202 so that the balloon 204 can maintain the carefully titrated balloon volume. The balloon 204 may be made of a suitable membrane to prevent the inflation fluid from diffusing across the membrane into the patient's vasculature. Also, the membrane may be designed to inflate and contract without undergoing a morphological change over time. However, as one skilled in the art will appreciate, the expandable blood flow regulator may be any catheter system, aortic isolation balloon system, or any vascular isolation balloon system known in the art for achieving partial REBOA.

[0038] Since the expandable blood flow regulator 200 only partially restricts aortic blood flow, it is possible to increase proximal blood pressure more physiologically while optimizing blood flow to downstream organs and tissue beds. Since aortic blood flow exceeds physiological requirements overall in the majority of cases of shock patients, minimal to moderate blockage minimizes ischemia. This tradeoff between proximal blood pressure increase and distal ischemia varies depending on the degree of shock and the patient's underlying physiological state. As will be appreciated by those skilled in the art, the catheter control device 400 can be operatively connected to any P-REBOA balloon catheter system, REBOA catheter system, aortic blockage balloon system, or other vascular blockage balloon system (e.g., IVC or iliac).

[0039] 3, the sensor 300 can measure physiological information indicative of aortic blood flow to determine the patient's baseline physiological condition. For example, the sensor 300 can measure physiological parameters including, but not limited to, blood pressure distal to the expandable flow regulator, blood pressure proximal to the expandable flow regulator, pressure within the expandable flow regulator, heart rate, respiratory rate, aortic blood flow proximal or distal to the expandable flow regulator, blood temperature, the patient's cardiac output, carotid blood flow, pulmonary artery pressure, peripheral vascular resistance, or intracranial pressure. The sensor 300 can include one or more sensors. For example, as shown in FIG. 3, the sensor 300 can include two sensors, a distal sensor 302 positioned to measure blood pressure from a blood pressure line inserted into a distal artery, and a sensor 304 positioned to measure blood pressure from a blood pressure line inserted into an artery proximal to the expandable flow regulator. For example, the distal sensor 302 can be connected, for example by a Luer lock connector, to a flush port on the expandable blood flow regulator introducer sheath or to an arterial line located in the contralateral femoral artery, and the proximal sensor 304 can be connected to a proximal blood pressure port on the expandable blood flow regulator or to a proximal blood pressure port on the proximal arterial line through the radial artery. Another sensor measuring the pressure within the expandable blood flow regulator 200 can be connected to the inflation port of the expandable blood flow regulator 200 to prevent overinflation and to facilitate detection of loss of pressure in the expandable blood flow regulator due to a bad connection or leak / rupture in the expandable blood flow regulator.

[0040] The sensor 300 can record data indicative of a physiological information measurement through analog or digital mechanisms, which can then be used to determine whether more or less restriction of aortic blood flow is necessary to maximize vital organ perfusion through automatic augmentation of blood pressure while simultaneously controlling bleeding, to reduce ischemia below the expansible flow regulator, and to reduce high blood pressure upstream of the expansible flow regulator, as described in more detail below.

[0041] The patient's physiological state can also be monitored by real-time and intermittent measurements of compounds in the patient's blood, serum, urine, or saliva, such as lactate levels, cortisol levels, reactive oxygen species levels, pH of bodily fluids, and other commonly used markers of the patient's physiological state.

[0042] 1 , the catheter control device 400 includes a processor 402 having a memory 404 and communications circuitry 406, and a pump 408. The processor 402 is operatively connectable to the sensor 300, a graphical user interface 410, and the pump 408, which is operatively connectable to the expandable flow regulator 200.

[0043] The processor 402 can receive data indicative of the physiological information measurements from the sensor 300 through the communication circuitry 406 and record the data in the memory 404. Additionally, the processor 402 can record waveforms corresponding to the physiological information measurements from the sensor 300 in the memory 404. The memory 404, e.g., a non-transitory computer readable medium, can store physiological target parameters and corresponding ranges related to aortic blood flow and instructions that, when executed by the processor 402, cause the processor 402 to determine whether the physiological information measurements are within the predetermined target physiological ranges by comparing the physiological information measurements to the target physiological ranges. The processor 402 can cause a graphical user interface 410, e.g., a touch-enabled LCD display, to display information indicative of the comparison of the physiological information measurements to the target physiological ranges. For example, the processor 402 can receive data indicative of blood pressure measurements distal to the expandable blood flow regulator 200 and blood pressure measurements proximal to the expandable blood flow regulator 200, from which the processor 402 can estimate aortic blood flow. Thus, the processor 402 can cause the graphical user interface 410 to display, e.g., graphically, the estimated aortic blood flow, as well as a physiological target parameter, e.g., a target aortic blood flow, and its desired corresponding range. For example, the graphical user interface 410 can display the target aortic blood flow at a centerline and a predetermined desired range above and below the centerline, e.g., in green, where the desired range is surrounded by a predetermined tolerance range, e.g., in yellow above and below the desired range, and the acceptable range is surrounded by a predetermined non-acceptable range, e.g., in red above and below the acceptable range. The graphical user interface 410 can display the estimated aortic blood flow in association with a range indicating whether the estimated aortic blood flow is outside of the desired and / or acceptable ranges. Thus, the processor 402 can calculate the appropriate change in the amount of obstruction by the expandable blood flow regulator 200 required to bring the patient's physiological condition within the target physiological range based on the patient's current physiological condition measurements.

[0044] Graphical user interface 410 allows the user to select various menu functions, such as a function to set a target aortic blood flow, a function to set an audible alarm indicating when blood flow is outside a desired range, a function to allow zeroing of sensor 300, and a function to allow input of patient information including, for example, height, weight, sex, name, and date of birth. Thus, memory 404 can store a patient profile corresponding to the patient information entered through graphical user interface 410. Information stored in memory 404 can be downloadable from catheter control device 400, for example, by a removable media card.

[0045] The processor 402 includes a series of sub-algorithms for controlling aspects of the proper inflation, deflation, and response to physiological changes of the balloon when the balloon catheter is in use. These individual algorithms may also calculate initial calibration to identify physical measurements of the blood vessel, determination of complete blockage, catheter operating range, e.g., identification of the range of blockage caused by changes in the patient's physiological condition, set point optimization, cessation of catheter-based physiological support, and adjustment of balloon volume.

[0046] The balloon catheter 200 undergoes a balloon calibration procedure upon initial catheter insertion or upon initiation of EPACC. The calibration procedure is also performed whenever a significant hemodynamic change not induced by EPACC is detected. At the start of the balloon calibration procedure, the pump 408 of the catheter control device 400 repeatedly introduces small aliquots of gas or fluid, e.g., carbon dioxide, saline, or a mixture of contrast and saline, into the balloon. During successive boluses, the proximal physiological condition can be monitored until a change is observed that indicates a low set point for the operating range of the balloon 204. The balloon 204 continues to inflate until the distal blood pressure waveform disappears or until no proximal physiological changes are observed that indicate the upper limit of the operating range of the balloon catheter 200. Alternatively, the upper limit can be indicated by measuring the cessation of aortic blood flow. The midpoint of the operating range can be set as an interval of balloon volume increase from the low set point and can be used as a criterion for a quick return to the operating range if necessary during EPACC.

[0047] After the balloon calibration is performed and the initial balloon volume set point is identified, the processor 402 causes the catheter control device 400 to adjust the shape and size of the expandable flow regulator 200 via the pump 408 to increase the proximal blood pressure in response to the patient's physiological condition. As described above, the processor 402 determines whether the physiological information measurement is within a predetermined target physiological range by comparing the physiological information measurement received from the sensor 300 with the target physiological range stored in the memory 404. For example, if the proximal blood pressure is set as the physiological marker, when the processor 402 determines that the proximal blood pressure has fallen below the target blood pressure range, the catheter control device 400 causes the pump 408 to expand the expandable blood flow regulator 200, e.g., to inflate the balloon. Similarly, when the processor 402 determines that the proximal blood pressure exceeds the target blood pressure range, the catheter control device 400 causes the pump 408 to deflate the expandable blood flow regulator 200, e.g., to deflate the balloon. The amount of change in balloon volume that occurs in response to an out-of-range blood pressure change depends on how far the current blood pressure measurement is from the target blood pressure. Thus, if the blood pressure is only minimally out of the target range, the size of the expansive flow regulator 200 is changed only slightly. In contrast, if the blood pressure is significantly out of the target range, the size of the expansive flow regulator 200 is changed more significantly. The processor 402 can record the amount of size change of the expansive flow regulator 200 caused by the pump 408 such that the memory 404 stores, for example, an ongoing tally of the balloon fill. Thus, a user can be provided with constant real-time information indicating, for example, how much fluid is in the balloon.

[0048] Exemplary algorithms that can be used to perform EPACC include: uL Bolus = (P0-P S ) J * V where P0 is the current blood pressure and P Sis the setpoint blood pressure, J is a constant, and V is a constant described below. Those skilled in the art will appreciate that alternative algorithms can be used to adjust the balloon volume based on the current and target physiological conditions. For example, alternative algorithms may use fewer or more than two constants and / or variables.

[0049] The balloon adjustment algorithm can dynamically control the magnitude of change in size of the expandable blood flow regulator 200 in response to the difference between the physiological information measurement and the physiological target parameter, for example, by constants V and J. Initially, V and J can be set to defaults, but V or J can be dynamically changed in response to the magnitude of the physiological change that occurs beyond the initial target set point. For example, if blood pressure is set as the physiological marker and the initial blood pressure stored by the sensor 300 is below the set point blood pressure, but the resulting blood pressure recorded by the sensor 300 after the pump 408 changes the amount of expansion of the expandable blood flow regulator 200 exceeds the set point blood pressure, V and / or J will be modified to correct for the exceedance of the target set point. If the blood pressure measurement is determined to be within the range of the target blood pressure, resulting in the amount of expansion of the expandable blood flow regulator 200 falling below the low set point, the expandable blood flow regulator 200 will shut off and return to its baseline zero set point. This can be done by deflating the balloon. For example, the following code shows the dynamic scaling of the expansion of the expandable blood flow regulator: TIFF0007660806000001.tif220159TIFF0007660806000002.tif175157

[0050] As described above, the processor 402 can automatically expand and contract the expandable blood flow regulator 200 through the pump 408 in accordance with the principles of the present disclosure. For example, if the expandable blood flow regulator 200 includes a balloon catheter, the pump 408 can be a syringe pump designed to inflate or deflate the balloon by injecting or removing fluid into or from the balloon through an outlet in fluid communication with the lumen of the catheter. The syringe pump can provide small titrated changes in balloon volume, e.g., in the range of 1-50 microliters, through automation in response to the patient's physiological condition. For example, the syringe pump can include a metallic threaded rod that allows linear movement of a syringe plunger guide. The syringe pump can be actuated by a low power consumption stepper motor, e.g., NEMA 11 or 8, and can include a reduction gearbox. In one embodiment, the syringe pump can be controlled by a linear actuator.

[0051] After each change in balloon volume by the pump 408 of the catheter control device 400, the processor 402 may wait a predetermined period of time to monitor the resulting physiological changes before further adjusting the balloon volume.

[0052] In one embodiment, pump 408 allows for manual inflation of the balloon, for example, when automation is unavailable or infeasible. For example, a manual pump may include a syringe pump that can inject fluid using the normal action of a syringe, but can also inject or remove fluid by screw action when threads on the plunger and in the barrel of the syringe are activated. Injecting by normal syringe plunging, but removing fluid only by screw action allows for rapid inflation of the balloon, but careful titration of removal of fluid based on the pitch of the threads on the plunger. As one of ordinary skill in the art will appreciate, manual pumps may include, for example, peristaltic pumps, rotary pumps, and the like.

[0053] In another embodiment, the catheter control device 400 can generate decision support when the physiological information measurements are outside of a predetermined target physiological range. The decision support (e.g., a set of instructions) can be communicated to the user (e.g., visually or audibly) via the graphical user interface 410, whereby the decision support guides the user to provide user input, for example, via the graphical user interface 410 or via a number of switches and / or buttons operatively connected to the processor 402. As one skilled in the art will appreciate, the graphical user interface 410 can include a number of switches and / or buttons for receiving user input. The user input can be sufficient to change the amount of blockage by the expandable flow regulator 200 required to bring the patient's physiological condition into the target physiological range based on the patient's current physiological condition measurements calculated by the processor 402. Thus, in response to receiving the user input, the processor 402 causes the pump 408 (e.g., a syringe pump) to inflate or deflate the balloon by injecting or removing fluid into or from the balloon through an outlet in fluid communication with the lumen of the catheter. The syringe pump can produce small, titrated changes in balloon volume, for example, in the range of 1 to 1000 microliters, in response to user input.

[0054] Figure 4 illustrates a conceptual embodiment of a catheter control device 400 having a graphical user interface 410 and in which the pump 408 is a syringe pump. As shown in Figure 4, the graphical user interface 410 may include a display 412 for visually conveying information to a user and a number of buttons and switches 414 for allowing a user to interact with the catheter control device 400, such as to expand or contract the expandable flow regulator 200 and / or navigate through menu functions provided by the graphical user interface 410.

[0055] An exemplary external central processing unit constructed in accordance with the principles of the present disclosure will now be described with reference to FIG. 5. As shown in FIG. 5, the external central processing unit 500 includes a processor 502 having a memory 504 and a communication circuit 506. In FIG. 5, the components of the processor 502 are not drawn to scale, either relative or absolute. The processor 502 may be constructed similarly to the processor 402 of the catheter control unit 400 of FIG. 1. Thus, the processor 502 is operatively connected to the sensor 300, receives data from the sensor 300 indicative of a physiological information measurement, and is capable of comparing the physiological information measurement to a target physiological range stored in the memory 504. When the system 100 includes the external central processing unit 500, the processor 502 of the external central processing unit 500 determines whether the physiological information measurement is within the target physiological range, calculates information indicative of an appropriate change in the amount of blockage by the expandable flow regulator 200 required to bring the patient's physiological condition within the target physiological range if the physiological information measurement is outside the target physiological range, and communicates the information to the catheter control unit 400 via the communication circuit 506. For example, the communication circuitry 506 of the external central processing unit 500 can communicate information to the communication circuitry 406 of the catheter control device 400 via at least one of WiFi, Bluetooth, Wixel-based communication, or cellular communication, or a wired connection, or other form of communication.

[0056] An exemplary method for dynamically adjusting the degree of aortic flow regulation in accordance with the principles of the present disclosure is described with reference to FIG. 6. Method 300 may be used to perform a partial aortic occlusion, e.g., P-REBOA, EVAC, or EPACC, for a patient suffering from, for example, septic or traumatic shock. In step 602, a distal end of a catheter is introduced into the patient through the femoral or radial artery, such that the distal end of the expandable flow regulator 200 is positioned within the aorta. As described above, the expandable flow regulator 200 may include a balloon catheter 200.

[0057] In step 604, the expandable aortic blood flow regulator 200 can expand to regulate blood flow in the aorta. For example, the drive mechanism 408 of the catheter control device 400 can inflate the balloon 204 of the balloon catheter 200 so that it regulates blood flow within the aorta.

[0058] In step 606, the sensor 300 can measure physiological information indicative of aortic blood flow. For example, as described above, the sensor 300 can measure information indicative of blood pressure distal to the expandable blood flow regulator, blood pressure proximal to the expandable blood flow regulator, pressure within the expandable blood flow regulator, heart rate, respiratory rate, aortic blood flow proximal or distal to the expandable blood flow regulator, blood temperature, the patient's cardiac output, carotid blood flow, pulmonary artery pressure, peripheral vascular resistance, or intracranial pressure. The sensor 300 can include one or more sensors positioned proximal and / or distal to the expandable blood flow regulator 200 to effectively monitor the patient's physiological condition. For example, one sensor can be positioned distal to the expandable blood flow regulator to measure blood pressure distal to the expandable blood flow regulator and another sensor can be positioned proximal to the expandable blood flow regulator to measure blood pressure proximal to the expandable blood flow regulator.

[0059] In step 608, the processor 402 of the catheter control device 400, or the processor 802 when utilizing the external central processing unit 500, may compare the measured physiological information to a target physiological range. In step 608, the processor 402 may first estimate the measured physiological information, e.g., aortic blood flow, from the blood pressure distal and proximal to the expandable flow regulator device and the corresponding waveform, and then compare the estimated aortic blood flow to a target physiological range, e.g., the target aortic blood flow. In step 610, the processor 402 determines whether the measured physiological information is within the target physiological range. If in step 610, the measured physiological information is determined to be within the target physiological range, the method 300 may maintain the current expansion state of the expandable flow regulator device 200 and return to step 606 to continue measuring the patient's physiological condition. If in step 610 it is determined that the physiological information measurement is outside the target physiological range, e.g., exceeds or is below the target physiological range, the processor 402 of the catheter control device 400 can determine the amount of change in expansion of the expandable blood flow regulation device 200 required to bring the patient's physiological condition within the target physiological range.

[0060] In step 612, the processor 402 prompts the drive mechanism 408 to adjust the expansion or contraction of the expandable blood flow regulation device, e.g., by inflating or deflating the balloon to adjust the blood flow rate in the aorta. In one embodiment, the drive mechanism 408 automatically adjusts the expansion or contraction of the expandable blood flow regulation device based on the amount of change in expansion of the expandable blood flow regulation device 200 required to bring the patient's physiological condition within the target physiological range, as determined by the processor 402. In another embodiment, in step 612, the processor 402 can generate a decision support available to a user to input user input, whereby the processor 402 prompts the drive mechanism 408 to adjust the expansion and contraction of the expandable blood flow regulation device based on the user input. During step 612, the processor 402 can issue an alert if the physiological information measurement is determined in step 610 to be outside the target physiological range, and the graphical user interface can prompt the alert to be communicated to the user, e.g., visually or audibly.

[0061] If an external central processing unit 500 is used, the processor 502 transmits information, determined in step 610, indicating the amount of change in expansion of the expandable blood flow regulating device 200 required to bring the patient's physiological condition within the target physiological range to the catheter control device 400 via the communications circuits 506 and 406, and then proceeds to step 612.

[0062] Test #1. EVAC Syringe Pump vs. Manually Controlled Pump The following experimental study, which involved in vivo animal testing of a custom-built hardware and software system for controlling aortic blood flow, was approved by the Institutional Animal Care and Use Committee at the David Grant Medical Center, Travis Air Force Base, California. Healthy adult castrated male and non-pregnant female Yorkshire crossbred pigs (Sus scrofa) were acclimated for a minimum of 7 days. Animals weighed between 60 and 95 kg at the time of the experiment.

[0063] The novel components of this platform include a combination of a precision automated syringe pump and a custom microcontroller that integrates physiological streaming data from the patient. Briefly, the hardware structure utilizes a commercially available microcontroller with wireless capabilities (available from Arduino, Somerville, MA) and a multi-channel 16-bit analog-to-digital converter for acquisition of physiological real-time data including aortic blood flow, proximal arterial pressure, and distal arterial pressure. The custom syringe pump utilized a NEMA 17 stepper motor driving a standard lead screw, a commercially available stepper motor controller (BigEasyDriver, available from Sparkfun, Newot, CO), custom 3D printed components to hold the syringe and plunger, and a wireless microcontroller for bidirectional communication with a master controller. Custom software was developed to precisely regulate aortic blood flow using a closed-loop feedback algorithm. A weight-based aortic blood flow of 4.3 mL / kg / min was established, which is approximately 10% of the baseline distal aortic blood flow.

[0064] Animals were premedicated with intramuscular tiletamine / zolazepam (TELAZOL, available from Fort Dodge Animal Health, Fort Dodge, IA) 6.6 mg / kg. After isoflurane induction and endotracheal intubation, general anesthesia was maintained with 2% isoflurane in 100% oxygen. To counteract the vasodilatory effects of general anesthesia, an intravenous infusion of norepinephrine (0.01 mg / kg / min) was started via venous access and titrated prior to the experiment to achieve a target mean arterial pressure of 65-75 mmHg. Animals were mechanically ventilated to maintain end-tidal CO2 at 40 ± 5 mmHg. Plasmalyte (available from Baxter, Deerfield, IL) maintenance infusion was administered intravenously at a flow rate of 10 mL / kg / h until abdominal closure, at which point the flow rate was reduced to 5 mL / kg / h for the remainder of the study to overcome insensible fluid loss. Heparin was administered intravenously to achieve an activated clotting time (ACT) of 100 seconds, similar to the human baseline value. Core body temperature was maintained at 35-37°C using an underbody warmer.

[0065] After laparotomy, a splenectomy was performed to minimize hemodynamic changes due to autologous blood transfusion. The left diaphragm was divided to expose the upper abdominal aorta and incised circumferentially at a length of 5–10 cm. A perivascular aortic flow probe (available from Transonic Systems Inc., Ithaca, NY) was placed distally with ligation of two adjacent intercostal arteries, which prevented intervening blood flow between the flow probe and the intravascular isolation balloon. The abdomen was closed with a cable tie. The external jugular vein was cannulated to facilitate medication and fluid administration. The right brachial artery was exposed and cannulated with a 7F sheath (SuperSheath, available from Boston Scientific, Marlborough, MA) for bleeding control. The left axillary artery was exposed and cannulated with a 9F sheath (SuperSheath, available from Boston Scientific, Marlborough, MA) for proximal arterial pressure monitoring. The left femoral artery was exposed and cannulated with a 12F sheath available from Teleflex Inc., Wayne, PA, through which a 9F Coda LP balloon (available from Cook Medical, Bloomington, IN) was advanced under fluoroscopic guidance to the level of the epigastric aorta just distal to the aortic blood flow probe (Zone 1). Distal pressure was also monitored through this sheath.

[0066] Physiological parameters and aortic blood flow measurements were collected in real time using a Biopac MP150 multichannel data acquisition system and a custom Arduino-based data acquisition system / controller (available from BioPac, Goleta, Calif.) Measured parameters included heart rate, blood pressure proximal and distal to the intra-aortic balloon, and aortic blood flow past the Zone I balloon.

[0067] Data analysis was performed and graphs constructed using Excel (available from Microsoft Corporation, Redmond, WA) and STATA version 14.0 (available from Stata Corporation, Bryan, TX). Continuous variables are graphed as mean and standard error of the mean. Categorical variables are presented as mean and standard deviation and standard error of the mean.

[0068] At the start of the experiment (T0), the animals were bled for 30 min with 25% of their total blood volume. After this 30 min bleed interval, the master controller initiated stepwise balloon inflations over approximately 3 min until the target weight-based blood flow rate was achieved. The EVAC syringe pump automatically adjusted the balloon volume to actively maintain aortic blood flow at this level for the duration of the 45 min EVAC interval. To confirm the performance of the EVAC syringe pump during active resuscitation, whole blood transfusion was initiated at T65. The EVAC syringe pump then initiated a 5 min balloon deflation and weaning sequence beginning at T75.

[0069] Five animals underwent instrumentation, hemorrhage, followed by 45 min of Zone 1 EVAC. All animals survived the experimental phase. As shown in Figures 7A-C, hemorrhage was associated with the expected decline in distal aortic blood flow and mean arterial pressure (e.g., proximal MAP and distal MAP) measured in both the proximal descending thoracic aorta and distal abdominal aorta. Upon initiation of EVAC at T30, there was an abrupt increase in proximal mean arterial pressure with a concomitant decrease in distal MAP. Also, as shown in Figure 7B, distal aortic pressure remained stable at approximately 16 mmHg throughout EVAC. Now referring to Figures 7C, 8C, and 8D, the EVAC syringe pump was able to maintain stable aortic blood flow throughout the 45 min intervention period while minimizing deviations from aortic blood flow targets.

[0070] As shown in Figure 8A, proximal MAP rose sharply at the start of transfusion at T65. The EVAC syringe pump responded with a compensatory increase in balloon volume to maintain the specified aortic blood flow. As a result of these compensatory balloon adjustments, both aortic blood flow and distal aortic pressure remained stable and unchanged during aggressive volume resuscitation.

[0071] The relationship between balloon volume and various hemodynamic parameters is shown in Figures 9A and 9B. The EVAC syringe pump produced small but discernible changes in balloon volume throughout the EVAC interval, while the largest changes occurred during the 10-minute transfusion period. Actual aortic blood flow approximated the target aortic blood flow (mean blood flow, 4.5 vs. 4.4 ml / kg / min). As shown in Figures 8D and 9A, the EVAC syringe pump maintained aortic blood flow within 11%-14% of baseline throughout the entire intervention period and at 13%-14% for more than 90% of the intervention period.

[0072] Gradual balloon deflation resulted in a rapid increase in aortic blood flow around the balloon. As shown in Figure 9A, a return to full baseline blood flow was observed after withdrawal of 2.5 mL from the balloon, and approximately twice the baseline blood flow was observed upon full balloon deflation (34 ml / kg / min and 67 ml / kg / min, respectively).

[0073] Throughout the 45 minute EVAC, the syringe pump performed an average of 537 balloon adjustments with an average balloon volume change of 6.4uL per adjustment. As shown in Table 1 below, the maximum average balloon volume change required to maintain blood flow within the specified range was approximately 100uL.

[0074] [Table 1]

[0075] Figures 9A and 9B show the control of balloon volume by an EVAC syringe pump in response to aortic blood flow and mean proximal arterial pressure, respectively, in one representative experiment. As a result of small, highly dynamic adjustments in balloon volume, blood flow remains essentially unchanged over time. Note that the balloon volume profile closely reflects the trend in mean proximal arterial pressure throughout the intervention.

[0076] This study is the first animal study of EVAC using a commercially available aortic cross-clamping catheter and a fully automated flow control device. It shows that precise aortic flow control is feasible and rapidly achievable with a commercially available aortic cross-clamping catheter by adjusting the cross-clamping balloon volume with an algorithm-driven automated syringe pump.

[0077] Early clinical trials have shown that P-REBOA is extremely challenging and produces unstable hemodynamics due to lack of fidelity with manual balloon titration. Furthermore, large animal models of P-REBOA have demonstrated a propensity for persistent ongoing bleeding. Continuing bleeding is a serious concern in any clinical setting, but especially so in scenarios with limited blood product supplies or when significant delays in surgical hemostasis are anticipated.

[0078] Thus, automation features were expected to improve the P-REBOA concept. The use of automation features addresses several major limitations of the manual approach to aortic blood flow regulation. First, the EVAC syringe pump is capable of performing very small changes in balloon filling volume. The current hardware design of the syringe pump is capable of delivering or withdrawing 10 uL aliquots of fluid at a time. These changes are too fine to be performed manually with any degree of fidelity or consistency and require robotic control. As shown in previous experiments and again in this experiment, very small adjustments in the blockade balloon volume translate into large changes in aortic blood flow. This hyperemic aortic blood flow was observed during the balloon deflation phase of the experiment and likely results from a combination of extremely high proximal aortic pressure and maximal vasodilation of the distal tissue bed. This hyperemic blood flow is fairly unpredictable in occurrence and occurs at different balloon volumes depending on the individual animal. Thus, precise control is required to prevent hemodynamic collapse or destabilization of the deposited clot and resumption of bleeding. Since balloon volume changes as small as 10 uL produce pronounced differences in aortic blood flow, it is clear why previous attempts at manual flow titration have resulted in unstable hemodynamics.

[0079] Furthermore, the EVAC syringe pump allows for dynamic changes in response to changing patient physiology through near-continuous adjustment of balloon volume. In this study, an average of approximately 600 balloon adjustments were made over a 45-minute period to maintain the desired aortic blood flow rate. This number of adjustments would be difficult, if not impossible, to achieve through manual control of balloon volume. Furthermore, humans are highly inefficient at integrating multiple streams of continuous data and responding in a timely manner with an appropriate measured response. However, computers and robots excel at these integration and computational tasks. Inefficiencies in care are amplified by allocating a skilled medical provider with the sole task of manually titrating the blockage balloon. This potential misallocation of critical medical expertise and manpower may prevent the adoption of partial aortic blockage as a resuscitation aid in austere environments.

[0080] The current EVAC syringe pump achieves a degree of aortic blood flow control comparable, if not superior, to previous extracorporeal blood flow regulation circuits. Previous approaches have shown that tight regulation of low distal aortic blood flow effectively reduces the ischemic burden of sustained aortic clamping while minimizing bleeding. However, one important consideration with this current software design is that titration is based on aortic blood flow data input. In the experiments, this data was obtained through the use of a surgically implanted perivascular blood flow probe, which is not clinically feasible. Unfortunately, there are no commercially available methods to obtain accurate measurements of aortic blood flow by minimally invasive or intravascular means that allow for careful titration of the balloon catheter. Despite this fact, the present study shows that distal aortic pressure and aortic blood flow are correlated in this particular model of bleeding and ischemia. It is therefore believed that titrating the degree of clamping to a particular distal aortic pressure will result in stable downstream aortic blood flow.

[0081] Test #2. EVAC vs. REBOA The following study comparing EVAC to REBOA was approved by The Institutional Animal Care and Use Committee at David Grant Medical Center, Travis Air Force Base. Referring now to FIG. 10, in this study, healthy adult castrated male and non-pregnant female Yorkshire crossbred swine (Sus scrofa) weighing 60-95 kg were bled for 25% of their total blood volume over 30 min, followed by block randomization to 45 min of treatment with Zone 1 or EVAC (n=6 per group). All animals then underwent resuscitation with the shed blood and underwent a protocolized critical care phase for the remainder of the 360 ​​min period, during which administration of vasopressors and isotonic fluids was automatically adjusted based on predefined physiological parameters.

[0082] Animals were premedicated with intramuscular tiletamine / zolazepam (TELAZOL, available from Fort Dodge Animal Health, Fort Dodge, IA) 6.6 mg / kg. After isoflurane induction and endotracheal intubation, general anesthesia was maintained with 2% isoflurane in 100% oxygen, with pulse oximetry maintained at 92–98% by titrating from 100% oxygen to 40% oxygen. To offset the vasodilatory effects of general anesthesia, an intravenous infusion of norepinephrine (0.01 mg / kg / min) was started via venous access and titrated prior to the experiment to achieve a target mean arterial pressure (MAP) of 65–75 mmHg. End-tidal CO2 was maintained at 40 ± 5 mmHg by mechanically ventilating the animals. All animals received a bolus of 1 liter Plasmalyte-A (available from Baxter, Deerfield, IL) at the time of venous access. After the bolus, Plasmalyte-A maintenance infusion was administered intravenously at a flow rate of 10 mL / kg / h until abdominal closure, then reduced to 5 mL / kg / h for the remainder of the study. Heparin was administered intravenously before the experiment to achieve an activated clotting time (ACT) of 100 seconds. Core body temperature was maintained at 35-37°C using an underbody warmer.

[0083] After laparotomy, a splenectomy was performed to minimize hemodynamic changes due to autologous blood transfusion. The upper abdominal aorta was exposed by dividing the left diaphragm, and the aorta was then incised circumferentially at a length of 5–10 cm. Two adjacent intercostal arteries were ligated, and a perivascular flow probe (available from Transonic Systems Inc., Ithaca, NY) was placed proximal to the ligated vessel to prevent intervening blood flow between the flow probe and the intravascular isolation balloon. The abdomen was closed with a cable tie, and vascular access was established as previously described. A 9F Coda LP balloon (available from Cook Medial LLC, Bloomington, IN) was positioned just distal to the aortic flow probe. The inflation syringe was connected to a custom-developed EVAC automated syringe pump capable of both full REBOA and EVAC.

[0084] After hemorrhage and subsequent randomization, animals in the EVAC arm demonstrated tightly controlled balloon-submerged aortic blood flow ranging from 1.5 to 4.4 ml / kg / min, e.g., 100 ml / min to 300 ml / min per 70 kg animal, for 45 min, which was achieved using a wireless automated syringe pump implementing a custom closed-loop feedback algorithm. In the REBOA arm, animals were subjected to 45 min of sustained total aortic clamping maintained by the same automated syringe pump.

[0085] From 80 minutes to the end of the study, intravenous crystalloid bolus administration and vasopressor titration were automated using a microcontroller interfaced with a standard peristaltic infusion pump and a custom infusion syringe pump, respectively. Fluid boluses were initiated based on continuous central venous pressure (CVP) and MAP values. Vasopressors were titrated upwards or downwards for hypotension (MAP < 60) or hypertension (MAP > 70), respectively. Animals were euthanized at T360 and immediately necropsied.

[0086] Physiological parameters and aortic blood flow measurements were collected in real time during the study using a multichannel data acquisition system (Biopac MP150, available from BioPac, Goleta, CA). Measured parameters included heart rate, blood pressure proximal and distal to the intra-aortic balloon catheter, central venous pressure, core temperature, and aortic blood flow. Arterial blood and urine were collected at predetermined intervals throughout the study for analysis. End organs were subjected to histological examination and analyzed by a blinded veterinary pathologist. Data analysis was performed with STATA version 14.0 (available from Stata Corporation, Bryan, TX). Continuous variables are presented as mean and standard error of the mean if normally distributed, or as median and interquartile range if not normally distributed, and analyzed using appropriate tests. Dichotomous and categorical variables were analyzed by Fisher's exact test and presented as percentages. Statistical significance was set at p<0.05.

[0087] As shown in Table 2 below, there were no differences in baseline characteristics, including hemodynamics, laboratory parameters, and baseline vasopressor requirements, between the groups.

[0088] [Table 2]

[0089] Referring now to Figures 11A-11C, REBOA and EVAC animals exhibited similar hypotensive responses to hemorrhage (33 mmHg 95CI 29-36 vs. 38 mmHg 95CI 32-44, respectively, p=0.08).

[0090] As shown in Table 3 below, during the intervention, REBOA animals had a significantly higher proximal MAP compared to EVAC (129mmHg 95CI 105-151 vs. 101mmHg 95CI 83-119, respectively, p=0.04), but there was no difference in peak MAP between the two groups. While there was no appreciable blood flow past the balloon during the intervention in the REBOA arm, EVAC animals showed a mean blood flow of 5.2mL / kg / min 95CI 4.86-5.62.

[0091] [Table 3] pMAP = mean proximal arterial pressure

[0092] During the critical care phase, EVAC animals maintained mean proximal MAP within the target range and demonstrated a higher global MAP than REBOA animals throughout this period. EVAC animals also demonstrated aortic blood flow closer to baseline values ​​during critical care compared to REBOA animals (36mL / kg / min 95CI 30-44 vs. 51mL / kg / min 95CI 41-61, p=0.01).

[0093] Referring now to Figures 12A and 12B, a significant difference in resuscitation requirements was observed during the critical care phase of the experiment. REBOA animals required more than twice the amount of crystalloid fluid compared to EVAC animals (7400ml 95CI 6148-8642 vs. 3450ml 95CI 1215-5684, p<0.01) in response to more frequent episodes of hypotension and low CVP compared to EVAC animals. Additionally, vasopressor requirements were significantly higher in REBOA animals (50.5ng / kg±5.3 vs. 21.5ng / kg±7.4, p=0.05).

[0094] One animal in the EVAC group experienced progressive hemodynamic deterioration during the critical care phase and died 40 minutes before the end of the study. Overall fluid and vasopressor requirements in this animal were 2 standard deviations higher than the mean fluid and vasopressor requirements for the entire EVAC cohort and 3 standard deviations higher than the five surviving EVAC animals. This animal was also the only animal in either group that demonstrated baseline aortic blood flow below the inclusion criteria before the initial pre-experiment fluid bolus, but met the aortic blood flow inclusion criteria after fluid administration and was therefore included in the study.

[0095] Referring now to Figure 13, both peak and final lactate levels were significantly lower in the EVAC group. There were no differences in hemoglobin values ​​between groups after resuscitation, and no differences in final creatinine levels between groups. Histological analysis showed no significant differences between REBOA and EVAC animals.

[0096] In this large animal hemorrhage model with an interventional window that reflects the current clinical use of REBOA, EVAC reduced distal ischemia and physiologic abnormalities compared to REBOA. This improvement is evidenced by lower serum lactate levels and reduced resuscitation requirements during the critical care phase. Furthermore, EVAC reduces the extremely high cardiac, pulmonary, and cerebral blood pressures produced by standard REBOA by increasing proximal pressure in a more physiologic manner during hemorrhagic shock. These beneficial physiologic outcomes were demonstrated over a clinically relevant occlusion period of 45 minutes. Finally, this study demonstrates that carefully titrated distal aortic blood flow is possible by combining an automated syringe pump with a standard, currently available aortic occlusion catheter.

[0097] In a previous proof-of-concept study, we utilized an extracorporeal circuit to precisely control distal aortic blood flow in a porcine liver injury model in which all control animals died within minutes. By using a 90-minute intervention period to mimic the realities of modern tactical evacuation on the battlefield, we recognized that application of a full REBOA would be infeasible in scenarios requiring prolonged intervention (>60 minutes). The degree of distal ischemia caused by a full aortic cross-clamp, e.g., REBOA, dramatically increased mortality and resuscitation requirements compared to animals given carefully titrated distal aortic blood flow. Importantly, this study demonstrated that as little as 10% of baseline aortic blood flow delivered by the EVAC device was sufficient to offset the deleterious effects of a full aortic cross-clamp, including distal ischemia induced by sustained full aortic cross-clamp as well as proximal supraphysiological aortic pressure and cardiac afterload. Furthermore, this prior study demonstrated that allowing 10% distal aortic blood flow during catastrophic and uncontrolled liver injury would not result in continued clot disruption and fatal hemorrhage. This was a marked departure from previous attempts to achieve partial aortic blood flow using manual titration in a similar model of liver injury, which was met with early mortality due to loss of control of downstream blood flow and subsequent continued hemorrhage.

[0098] These initial experiments suggested that titration of aortic blood flow may be a feasible approach to extend the benefits of REBOA over prolonged interventional periods. However, these preliminary studies did not address the more typical scenario of in-hospital application of REBOA, where maximum occlusion times are usually limited to less than 60 minutes. There is no existing clinical or translational data for these shorter occlusion periods, suggesting that a partial flow strategy would show physiological advantages over complete aortic cross-clamping. This study sought to address this important concern regarding the clinical applicability of EVAC in modern scenarios. In a short interventional period of 45 minutes, EVAC still produced relatively modest increases in physiological proximal pressures, dramatically reducing the physiological impact of sustained aortic cross-clamping. After resuscitation, both fluid and vasopressor requirements were less than half of those after REBOA. Furthermore, EVAC produced less hyperemic blood flow throughout the entire critical care phase, as evidenced by the lower aortic blood flow during the critical care phase. Presumably, this finding reflects a reduced physiological burden of this intervention. Overall, this study provides experimental support for the EVAC partial flow strategy during an intervention period that reflects typical in-hospital use.

[0099] Accumulating clinical evidence suggests that applying REBOA at or after cardiac arrest results in poor survival rates comparable to the poor survival rates in patients undergoing resuscitative thoracotomy. Conversely, applying REBOA before hemodynamic collapse has been shown to improve survival rates. Thus, earlier intervention during resuscitation efforts should be a priority in the overall management of this patient population. Based on the improved ischemic profile and physiologic response that EVAC provides, this strategy could theoretically be applied prior to the threshold at which REBOA is utilized. Such use could not only improve survival rates during trauma resuscitation, but also advantageously minimize morbidity by reducing the well-described downstream consequences of large volumes of fluids, vasopressors, and crystalloids.

[0100] Through continued technological development, a viable strategy has been refined to achieve controlled titrated distal aortic blood flow using a conventional compliant balloon catheter inflated with an automated syringe pump. This pump and controller represent a major advancement. Given the complex interplay of blood pressure, cardiac output, vascular tone, and other neuroendocrine factors, precise control of aortic blood flow with EVAC requires automation using closed-loop feedback where small changes in balloon volume are implemented in real time beyond the capabilities of manual control. The automated syringe pump utilized in this study is capable of near-continuous microliter-sized balloon volume adjustments. The development of this experimental EVAC syringe pump further advances the art toward a clinically relevant endovascular device for the management of noncompressible truncal hemorrhage.

[0101] The only death in this study was in the EVAC test arm, but it is important to emphasize that this animal was an outlier in the data, requiring relatively significant higher fluid and vasopressor requirements. This study is a subset of a broader study encompassing six randomized arms evaluating several derivative applications of this technology. This was the only animal out of approximately 60 that did not survive the study period. Despite being an outlier, all physiological and laboratory data from this animal were incorporated into the analysis, which certainly reduces the overall differences between groups. Nevertheless, this study showed significant differences between groups across multiple physiological and biochemical endpoints. This only strengthens the perceived advantages of EVAC over REBOA.

[0102] There are several limitations to the present study. First, this was a non-survival study with a total experimental time of only 6 hours. Presumably, definitive differences between groups regarding physiology or tissue status will become evident with longer duration studies. Nevertheless, the fidelity of the EVAC syringe pump to deliver stable aortic blood flow, especially during active resuscitation with whole blood at the end of the intervention period, was comparable to existing extracorporeal blood flow circuit models. The current hardware implementation for generating EVAC by endovascular means is experimental, and aortic blood flow is adjusted based on direct aortic blood flow measurements with a perivascular probe surrounding the upper abdominal aorta. However, consistent with previous reports, a strong correlation exists between distal aortic pressure and downstream aortic blood flow beyond the balloon, especially at the low blood flow rates targeted in the present study. This suggests that distal blood pressure may serve as a viable surrogate metric of aortic blood flow by which to clinically adjust EVAC. Despite these limitations, these results indicate a significant technical and technological advancement in mitigating the adverse outcomes of REBOA while maintaining its life-saving benefits.

[0103] Although various exemplary aspects of the present disclosure have been described above, it will be apparent to one skilled in the art that various changes and modifications can be made to the present disclosure without departing from the present disclosure. It is intended that the appended claims cover all such changes and modifications that fall within the true scope of the present disclosure.

Claims

1. A control device for an expandable blood flow control device for automating expansion and contraction of an expandable blood flow control device disposed in a blood vessel to partially restrict blood flow through the blood vessel, the expandable blood flow control device being disposed in a distal end region of a catheter, the control device comprising: a pump in fluid communication with the expandable flow control device via the catheter, the pump configured to expand and contract the expandable flow control device within the blood vessel; A processor; A non-transitory computer readable medium storing instructions that, when executed by a processor when the processor is operatively connected to a first blood pressure sensor positioned distal to the expandable blood flow regulator and a second blood pressure sensor positioned proximal to the expandable blood flow regulator, cause the processor to: receiving a physiological information measurement distal to the expansible blood flow regulator from the first blood pressure sensor; receiving a physiological information measurement proximal to the expandable flow regulator from the second blood pressure sensor; comparing the physiological information measurements from at least one of the first blood pressure sensor and the second blood pressure sensor to a target physiological range to determine whether the physiological information measurements from at least one of the first blood pressure sensor and the second blood pressure sensor are within the target physiological range; calculating a first difference between the physiological information measurement from the first blood pressure sensor or the second blood pressure sensor and a set point within the target physiological range; setting a dynamic scaling factor to a default, and then varying the dynamic scaling factor so that its value is responsive to a magnitude of the first difference between the physiological information measurement from the first blood pressure sensor or the second blood pressure sensor and the set point within the target physiological range; calculating the bolus amount according to a formula using at least the dynamic scaling factor; and causing the pump to adjust the expansion or contraction of the expandable blood flow regulator by the bolus amount to adjust blood flow in the blood vessel when the physiological information measurement from at least one of the first blood pressure sensor and the second blood pressure sensor is outside the target physiological range; A non-transitory computer-readable medium; A control device comprising:

2. 2. The control device of claim 1, wherein the expandable blood flow regulation device includes a balloon configured to expand to restrict blood flow in a blood vessel, and the pump is configured to inflate or deflate the balloon to regulate blood flow in the blood vessel when the physiological information measurement from at least one of the first blood pressure sensor and the second blood pressure sensor is outside the target physiological range.

3. The control device of claim 2 , wherein the pump is configured to inflate or deflate the balloon by delivering a bolus volume as small as 1 microliter.

4. The control device of claim 2 , wherein the pump is configured to inflate or deflate the balloon via a stepper motor connected to the processor.

5. The control device of claim 1, wherein the processor, based on the comparison, causes the pump to automatically adjust the expansion or contraction of the expandable blood flow regulating device to regulate blood flow in the blood vessel when the physiological information measurement from at least one of the first blood pressure sensor and the second blood pressure sensor is outside the target physiological range.

6. 2. The control device of claim 1, further comprising a plurality of switches and / or buttons operatively connected to the processor, the processor, in response to user input received via the plurality of switches and / or buttons, causing the pump to adjust the expansion or contraction of the expandable blood flow regulating device to regulate blood flow in the blood vessel when the physiological information measurement from at least one of the first blood pressure sensor and the second blood pressure sensor is outside the target physiological range.

7. The controller of claim 1 , further comprising a graphical user interface configured to display information indicative of the comparison.

8. The control device of claim 7 , wherein the graphical user interface is further configured to audibly communicate decision support based on the comparison such that a user can provide user input based on the decision support.

9. The control device of claim 1 , wherein the processor issues an alarm if the physiological information measurement from at least one of the first blood pressure sensor and the second blood pressure sensor is outside the target physiological range.

10. A precision control system for partial occlusion of an aorta, comprising the control device according to claim 1, the expandable blood flow control device disposed at the distal end of the catheter; the first blood pressure sensor; and The second blood pressure sensor The system further comprises:

11. 11. The system of claim 10, further comprising one or more additional sensors operatively connected to the processor and configured to measure at least one of the pressure within the expandable flow regulator, heart rate, respiratory rate, blood temperature, the patient's cardiac output, carotid blood flow, pulmonary artery pressure, peripheral vascular resistance, or intracranial pressure.

12. 11. The system of claim 10, further comprising an external central processing unit operatively connected to the control unit and the first and second blood pressure sensors, the external central processing unit configured to communicate information to the control unit indicative of whether the physiological information measurements from at least one of the first blood pressure sensor and the second blood pressure sensor are outside the target physiological range.

13. 13. The system of claim 12, wherein the external central processing unit communicates the information to the controller through at least one of WiFi, Bluetooth, Wixel-based communication, cellular communication, or other forms of communication.

14. The control device of claim 1 , wherein the physiological information measurement comprises a waveform of a blood pressure measurement.

15. The control device of claim 1 , wherein the dynamic scaling factor is based on one or more of a change in the physiological information measurement from the first blood pressure sensor and a change in the physiological information measurement from the second blood pressure sensor.

16. The instructions, when executed by the processor, further cause the processor to: and first allowing the pump to adjust the expansion or contraction of the expandable blood flow regulator before calculating the dynamic scaling factor. The control device according to claim 1.

17. The instructions, when executed by the processor, further cause the processor to: Determine that the time dilation has elapsed, receiving subsequent physiological information measurements from the first blood pressure sensor and the second blood pressure sensor after causing the pump to adjust the contraction or expansion of the expansive blood flow regulator by the bolus amount and in response to determining that the time delay has elapsed; and calculating a second difference between the subsequent physiological information measurement from at least one of the first blood pressure sensor and the second blood pressure sensor and the target physiological range; The control device according to claim 1.

18. The bolus amount is a first bolus amount, and the instructions, when executed by the processor, further cause the processor to: further varying the dynamic scaling factor such that the value of the dynamic scaling factor is a value responsive to the magnitude of the second difference; and calculating a second bolus amount according to the formula using the changed dynamic scaling factor; 18. The control device of claim 17.

19. The control device of claim 17 , wherein the time delay is based on the first difference.

20. The control device of claim 2 , wherein the pump is configured to deliver a bolus volume of 1-50 microliters to inflate or deflate the balloon.

21. The control device of claim 4 , wherein the pump is a syringe pump.

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