Patent Publication Number: US-2013231593-A1

Title: Non-invasive system to regulate intracranial pressure

Description:
CROSS REFERENCES TO RELATED APPLICATIONS 
     This application claims the benefit of U.S. Provisional Application No. 61/606,153, filed Mar. 2, 2012, the complete disclosure of which is herein incorporated by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     This invention relates generally to the field of non-invasive treatments, and in particular to the reduction of intracranial pressures and brain swelling. 
     BRIEF SUMMARY OF THE INVENTION 
     Elevated intracranial pressure is a leading cause of brain damage and death in patients with a stroke, cerebral bleed, brain surgery, cardiac arrest, brain edema, and other forms of traumatic and non-traumatic brain injury. Treatment options, especially non-invasive treatment options, are limited. This invention provides a novel systems to non-invasively reduce elevated intracranial pressure and brain edema. 
     More specifically, in one exemplary embodiment a method is provided for non-invasively lowering a person&#39;s ICP and increasing cerebral perfusion pressure. The method may include the step of actively lowering the person&#39;s intrathoracic pressure. Also, the person&#39;s effective circulating blood volume is lowered while the person&#39;s intrathoracic pressure is lowered to thereby non-invasively reduce venous blood volume in the brain to treat elevated intracranial pressure and/or brain edema. 
     In one step, the person&#39;s effective circulating blood volume is reduced by utilizing a lower body negative pressure (LBNP) apparatus. The person&#39;s intrathoracic pressure may be lowered by preventing air from entering the lungs while lifting the chest and/or by actively removing air from the lungs. In another step, the person&#39;s effective circulating blood volume and/or intrathoracic pressure are altered using at least one physiological parameter to guide the therapy. Further, the person may be suffering from brain injury secondary to stroke, cerebral bleed, brain surgery, cardiac arrest, brain edema, brain swelling, brain lymphedema, and other forms of traumatic and non-traumatic brain injury. 
     In another embodiment, the invention provides a device to non-invasively lower ICP and increase cerebral perfusion pressure that non-invasively reduces venous blood volume in the brain that encircles the lower body and can be used to generate LBNP. 
     In a further embodiment, a system is provided to non-invasively lower ICP and increase cerebral perfusion pressure. The system comprises a device to actively lower the person&#39;s intrathoracic pressure, and a device to lower the person&#39;s effective circulating blood volume while the person&#39;s intrathoracic pressure is lowered to thereby reduce venous blood volume in the brain to treat elevated intracranial pressure. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  illustrates one embodiment of a system that may be used to manipulate intrathoracic pressures using a resistor valve (also referred to herein as an ITD) according to the invention. 
         FIG. 2  illustrates another embodiment of a system that may be used to manipulate intrathoracic pressures using a resistor valve (ITD), particularly when the person is breathing. 
         FIG. 3  illustrates still another embodiment of a system that may be used to manipulate intrathoracic pressures using an intrathoracic pressure regulator (also referred to herein as an ITPR) according to the invention. 
         FIG. 4  is a graph illustrating the manipulation of intrathoracic pressures while the person&#39;s circulating blood volume is lowered in order to lower intracranial pressures. 
         FIG. 5  illustrates a machine to lower body native pressure (in order to effectively lower circulating blood volume) that is used in combination with an ITD. 
         FIG. 6  is a flow chart illustrating one embodiment of a method for non-invasively lowering a person&#39;s ICP and increasing cerebral perfusion according to the invention. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The devices and methods in this application provide a systems, devices and methods to non-invasively 1) reduce total circulating blood volume and 2) lower intrathoracic pressure in order to lower intracranial pressure (ICP) and improve brain perfusion by reducing the volume of venous blood in the brain and simultaneously providing sufficient venous volume in the thorax to maintain adequate or enhanced circulation to and through the heart. A variety of techniques and equipment may be used to reduce total circulating blood volume and to lower intrathoracic pressure. 
     For example, intrathoracic pressures may be reduced in both breathing and non-breathing patients. For patients that are spontaneously breathing, a valve or other mechanism to block the inflow of air into the lungs when inspiring may be used. As one example a pressure responsive valve (or ITD) may be employed. Such a valve prevents or resists the flow of air into the lungs when the patient attempts to inhale. If a certain negative intrathoracic pressure is obtained, the valve opens to provide ventilation to the patient. As another example, an intrathoracic pressure regulator (ITPR) could be used. The regulator may be constructed of a vacuum or other pressure source (including a ventilator) that applies a negative pressure or resistance as the person attempts in inspire. 
     For those not breathing, the person&#39;s chest could be actively lifted or the person induced to gasp while connected to an ITD. As another option, after a positive pressure breath from a mechanical ventilator, respiratory gases may be extracted from the lungs to create a lower the intrathoracic pressure. 
     Various techniques to lower intrathoracic pressure for both breathing and non-breathing patients are described in U.S. Pat. Nos. 5,551,420; 5,692,498; 6,062,219; 6,526,973; 6,604,523; 7,210,480; 6,986,349; 7,204,251; 5,730,122; 7,195,012; 7,185,649; 7,082,945; 7,195,013, 7,836,881; 7,766,011; 6,938,618; 7,275,542; 8,011,367; and U.S. Patent Publication Nos. 2010/0319691 and 2011/0098612, and in  A  &amp;  A , January 2007 vol. 104 no. 1 157-162, Intrathoracic Pressure Regulation Improves 24-Hour survival in a Porcine Model of Hypovolemic Shock, Demetris Yannopoulos, MD, Scott McKnite, BSc, Anja Metzger, PhD and Keith G. Lurie, MD, and  Resuscitation,  2006 September; 70(3):445-53.  Epub  2006 Aug. 9, Intrathoracic pressure regulation improves vital organ perfusion pressures in normovolemic and hypovolemic pigs, Yannopoulos D, Metzger A, McKnite S, Nadkarni V, Aufderheide T P, Idris A, Dries D, Benditt D G, Lurie K G. The complete disclosures of all of these references are herein incorporated by reference. 
     As previously described, one exemplary way to lower intrathoracic pressures in both spontaneously breathing and non-breathing subjects is by use of a resistor valve, a pressure valve, or the like (also referred to herein as an ITD). Examples of systems incorporating ITDs are shown in  FIGS. 1 and 2 . Referring first to  FIG. 1 , one embodiment of a system  10  for lowering intrathoracic pressure will be described. System  10  comprises an ITD  12  that is coupled to a ventilatory bag  14  at one end and an endotracheal tube  16  at the other end. An interface  18  that fits around the patient&#39;s mouth along with a head strap  20  may be used to secure endotracheal tube  16  in the desired position. Although shown with an endotracheal tube, it will be appreciated that other patient interfaces could be used, such as a facial mask, laryngeal mask, or the like. ITD  12  comprises a housing  22  that contains a pressure responsive valve (hidden from view). The pressure responsive valve is configured to be in a closed position when the patient&#39;s chest is actively lifted (such as when performing ACD CPR) or when the patient is inspiring. In this way, air is prevented from entering the lungs to increase the amount of negative intrathoracic pressure. In the event that the negative intrathoracic pressure becomes too great, the pressure-responsive valve is configured to open to allow air to flow to the lungs. Upon exhalation, respiratory gases from the lungs are allowed to freely pass through housing  22  and out exit port  24 . When needed, ventilation may be provided by squeezing bag  14  which allows respiratory gases to flow through housing  22  and into the lungs. It will be appreciated that other ventilation sources could also be used. 
     Hence, with system  10  a person&#39;s intrathoracic pressure may be lowered each time a patient attempts to inhale, when the person&#39;s chest is actively lifted, when the patient is caused to gasp, and the like. System  10  may be used in combination with any mechanism or technique that effectively lowers the patient&#39;s blood circulation to thereby reduce ICP. 
       FIG. 2  illustrates a system  200  that may be used to lower a person&#39;s intrathoracic pressure while breathing. System  200  includes an ITD  202  that is coupled to a facial mask  204 . ITD  202  may be constructed in a similar manner to ITD  12  of  FIG. 1 . In this manner, when mask  204  is coupled to a person&#39;s face and the person breathes, air will be prevented from reaching the lungs during each attempted inspiration. This causes the person&#39;s intrathoracic pressure to lower during each attempted inhalation. In the event that the negative intrathoracic pressure becomes too great, the pressure-responsive valve is configured to open to allow air to flow to the lungs. Upon exhalation, respiratory gases from the lungs are allowed to freely pass through ITD  202  and out an exit port  206 . A ventilator gas can also be provided through a line  208 . 
     Exemplary resistor valves, including those similar to ITDs  12  and  202 , are described in U.S. Pat. Nos. 5,551,420; 5,692,498; 6,062,219; 6,526,973; 6,604,523; 7,210,480; 6,986,349; 7,204,251; 5,730,122; 7,195,012; 7,185,649; 7,082,945; 7,195,013, 7,836,881; 7,766,011; 6,938,618; 7,275,542; 8,011,367, previously incorporated by reference. 
     For the non-breathing patient a lower level negative intrathoracic pressure may be generated after each positive pressure breath with an intrathoracic pressure regulator (ITPR). An example of an intrathoracic pressure regulation system  300  is shown in  FIG. 3 . System  300  may be constructed of a valve system  302  that is coupled to an endotracheal tube  304  that interfaces with the patient&#39;s lungs. An interface  306  that fits around the patient&#39;s mouth along with a head strap  308  may be used to secure endotracheal tube  304  in the desired position. Although shown with an endotracheal tube, it will be appreciated that other patient interfaces could be used, such as a facial mask, laryngeal mask, or the like. 
     System  300  further includes a manifold  310  that is fluidly coupled to valve system  302  and to a ventilator bag  312  (or other source of respiratory gases). Also coupled to manifold  310  is a vacuum line  316  that is in fluid communication with a vacuum source  318 . A safety valve  320  is also coupled to manifold  310 . 
     In operation, a continuous vacuum is created using vacuum source  318 , creating a negative pressure within manifold  310 . In turn, this causes respiratory gases to be evacuated from the person&#39;s lungs via endotracheal tube  304  and valve system  303 . In this way, the person&#39;s intrathoracic pressure may be lowered. In the event the intrathoracic pressure is lowered below a threshold level, safety valve  320  opens to lower the pressure in manifold  310  and reduce the vacuum applied to the lungs. The patient may be periodically ventilated by squeezing bag  312  which cases a positive pressure breath to pass through manifold  310 , through valve system  302  and into the lungs. 
     Hence, system  300  provides a way to lower the intrathoracic pressure of a non-breathing person while also providing periodic ventilation. System  300  may be used in combination with any mechanism or technique that effectively lowers the patient&#39;s blood circulation to thereby reduce ICP. 
     In some cases, system  300  could also be used with a breathing person, where the vacuum or negative pressure is applied at least periodically to the person&#39;s lungs (such as with a ventilator) so that as the person attempts to inhale, the resistance is increased thereby lowering intrathoracic pressure. 
     Examples of ITPR&#39;s, such as the one used in system  300 , are also described in U.S. Published Application Nos. 2010/0319691 and 2011/0098612, and in  A  &amp;  A , January 2007 vol. 104 no. 1 157-162, Intrathoracic Pressure Regulation Improves 24-Hour survival in a Porcine Model of Hypovolemic Shock, Demetris Yannopoulos, MD, Scott McKnite, BSc, Anja Metzger, PhD and Keith G. Lurie, MD, and  Resuscitation,  2006 September; 70(3):445-53 . Epub  2006 Aug. 9, Intrathoracic pressure regulation improves vital organ perfusion pressures in normovolemic and hypovolemic pigs, Yannopoulos D, Metzger A, McKnite S, Nadkarni V, Aufderheide T P, Idris A, Dries D, Benditt D G, Lurie K G, previously incorporated herein by reference. 
     One example how a person&#39;s intrathoracic pressure is lowered using an ITD or ITPR is illustrated in  FIG. 4 . In  FIG. 4 , when the person exhales, the intrathoracic pressure is generally positive. However, as the person inhales (or the chest is actively lifted), respiratory gases are prevented or hindered from entering the lungs, thereby reducing the intrathoracic pressure. A similar result may be achieved using an ITPR where gases are actively extracted from the lungs. In combination with the lowering of intrathoracic pressure, the person&#39;s effective blood circulation may be lowered, such as by drawing blood into the lower extremities. In this way, the person&#39;s ICP may be lowered as described herein. 
     One aspect of the invention uses such methods and devices, including those described above as ITD or ITPR therapy, together with ways to decrease circulating blood volume. In other words, a person&#39;s effective circulating blood volume is lowered in combination with lowering the person&#39;s intrathoracic pressure in order to lower a person&#39;s ICP and increase cerebral perfusion pressure. One way to reduce circulating blood volume is with a lower body negative pressure (LBNP) chamber or similar device. Such devices are used to study the effects of g-forces by the military and NASA and the effects of simulated blood loss by research scientists. 
     One embodiment of an LBNP  500  is shown in  FIG. 5 . LBNP is constructed of a chamber  502  having an entrance  503  through which the person&#39;s lower body is placed. A support surface  504  is employed to support the user&#39;s body while being positioned as shown in  FIG. 5 . Entrance  503  may include a seal that tightly fits around the person&#39;s waist or lower torso to provide an airtight seal between the person&#39;s body and the outside environment. In this way, a vacuum may be applied to the chamber  502 . In so doing, the pressure surrounding the person&#39;s lower body is reduced to draw blood from the thorax and into the lower extremities, thereby effectively reducing the person&#39;s circulating blood volume. In other words, more of the person&#39;s blood is stored in the lower extremities. 
     LBNP may be used alone in order to reduce ICP and increase coronary perfusion pressure. Alternatively, LBNP  500  may be used in combination with an ITD or ITPR therapy, including the devices and systems illustrated in  FIGS. 1-3 . For example, as shown in  FIG. 5  the patient is utilizing system  200 , including ITD  202  and facial mask  204 . With facial mask  204  sealed to the person&#39;s face, the person breathes through ITD  202  to lower the intrathoracic pressure as previously described. At the same time, the person&#39;s effective circulating blood volume is reduced, thereby using two mechanisms to reduce ICP and increase coronary perfusion pressure. 
     Optionally, one or more sensors (such as sensor  510 ) may be used to monitor various physiological parameters. For example, sensor may be used to monitor blood pressure, ICP, other measures of blood flow, and the like. Data from these sensors may be used to regulate the level of the vacuum in LBNP  500 . This may be done in an automated manner using a computer system. This data may also be used to notify the medical caregiver about the levels of intrathoracic pressure, whether the ITD or ITPR therapy should be adjusted and/or to modify the settings on the equipment used to manipulate intrathoracic pressures. 
     Use of a lower body negative pressure chamber by itself as a therapy or in combination with ITD or ITPR for the treatment of the clinical problem of increased intracranial pressure and brain edema is critical. The LBNP alone or in combination with an ITD or ITPR device provides way to treat patients suffering from a variety of ailments and conditions, such as brain edema, stroke, cerebral bleed, brain surgery, cardiac arrest, and other forms of traumatic and non-traumatic brain injury. 
     In one embodiment, the LBNP device is regulated to provide continuous, graded, pulsatile or intermittent LBNP and may be regulated either independently or in concert with the ITPR or ITD device. This could be accomplished by using a computer controller that controls operation of the LBNP device as well as any device used to lower intrathoracic pressure. The regulation may be linked to one or more physiological measurements that are made on the patient. These measurements may be taken by sensors or other detectors and transmitted to the computer controller having one or more processors and associated memory and software in order to modify the treatment, including the parameters for the LBNP device and the ITD or ITPR device. The LBNP chamber may be connected to an independent power source to regulate the vacuum or a self-contained unit. The LBNP unit may be designed to fit one size or many different sized patients. 
     One LBNP embodiment may comprise a self-contained unit that surrounds the subject&#39;s legs and fits around the subject with a tight seal or gasket at the level of the waist or lower abdomen. A regulation system, such as the computer controller, may be employed to generate continuous or intermittent negative pressure within this chamber from between about −5 to about −100 mmHg to draw blood into the lower body and thus reduce the effective circulating blood volume. Additional ways to alter LBNP may be provided intermittently to prevent stagnation of blood in the lower body, including in one embodiment the use of intermittent compression of the lower extremities when still subjected to LBNP. In one embodiment LBNP may be used, and regulated simultaneously, with an ITD or ITPR device to lower ICP and increase circulation to the brain and heart. In such an embodiment, the LBNP reduces circulating blood volume to the brain and the ITPR and ITD draws more blood back to the thorax and out of the brain. The combined physiological mechanisms increase cardiac filling, cardiac output, and systemic blood pressure while simultaneously lowering brain pressures, especially ICP and cerebral venous pressures. The net effect is to increase cerebral perfusion and lower ICP. Such an embodiment also reduces brain edema by actively drawing fluid out of the brain cells due to the reduction in cerebral venous pressure. Physiological monitoring of blood pressure and/or ICP or other measures of blood flow can be used to regulate the level of the vacuum in the LBNP and the changes of intrathoracic pressure generated by the ITD or ITPR. This may be done using a computer system or controller as previously described. For example, if the systemic blood pressure is too low, a closed loop computer algorithm can be used that takes the blood pressure information and regulates the level of LBNP and/or negative intrathoracic pressure generated by the ITPR and thereby increase systemic pressures. 
     Also, in some cases a LBNP system may be used to apply a vacuum to one and/or two legs at a time, or simultaneously to the entire lower body. Also, an ongoing shrink wrap may be used with the same body parts. In a further alternative, invasive techniques may be used to lower blood volume, including by physically removing blood from the body. This blood may be temporarily saved and preserved (such as by continuous oxygenation) so that it may be reintroduced back into the patient following a procedure where changes in intrathoracic pressures are manipulated (such as by using the ITD or ITPR as previously described). 
     Referring now to  FIG. 6 , one exemplary method  600  for lowering a person&#39;s ICP and increasing cerebral perfusion will be described. As illustrated in step  602 , The person&#39;s effective circulating blood volume is reduced in order to treat elevated intracranial pressure and/or brain edema. This may be accomplished, for example, by using a lower body negative pressure device. In some cases, this step may be performed alone, without any of the subsequent steps. 
     In some cases, and as illustrated in step  604 , the person&#39;s intrathoracic pressure may be actively lowered. This may be performed in combination with step  602  such that while the person&#39;s circulating blood volume is in a reduced state, the person&#39;s intrathoracic pressure may also be lowered. This may be accomplished, for example, by preventing air from entering the lungs while breathing through a pressure responsive valve, by preventing air from entering the lungs while actively lifting the person&#39;s chest, or actively removing air from the lungs. 
     Optionally, as illustrated in step  606 , one or more physiological parameters may be measured and used to regulate the person&#39;s circulating blood volume and/or intrathoracic pressure. This may be accomplished, for example, by using various sensors that feed data to a computer system that may in turn be used to control any equipment used to reduce the person&#39;s lower body pressure and/or to reduce the person&#39;s intrathoracic pressure. 
     The invention has now been described in detail for purposes of clarity and understanding. However, it will be appreciated that certain changes and modifications may be practiced within the scope of the appended claims.