WO2016049534A1

WO2016049534A1 - Brain cooling devices and methods

Info

Publication number: WO2016049534A1
Application number: PCT/US2015/052369
Authority: WO
Inventors: Thomas Kreck; Seth Rodgers; Andrew Scott
Original assignee: Neurosave, Inc.
Priority date: 2014-09-26
Filing date: 2015-09-25
Publication date: 2016-03-31

Abstract

Cooling devices and method, such as those, for example, configured to cool the brain of a subject. This disclosure includes embodiments of cooling devices and methods configured to cool the brain of a subject. Such devices are configurable to be stationary or substantially stationary in some embodiments (e.g., used in hospitals, medical clinics, and any other health care facility), and in other embodiments, the devices of this disclosure can be mobile/transportable (e.g., used at the scene of an accident, used in an ambulance, helicopter, or other vehicle used to provide health care, and the like). Further, methods described in this disclosure can be continuous, intermittent, or a combination thereof, depending on the circumstances.

Description

DESCRIPTION

BRAIN COOLING DEVICES AND METHODS

[0001] This application claims priority to United States Provisional Patent

Application No. 62/056,304 filed September 26, 2014, which is incorporated herein by reference in its entirety.

BACKGROUND

1. Field of the Invention

[0002] The present invention relates generally to cooling devices and method, and more particularly, but not by way of limitation, to cooling devices and methods configured to cool the brain of a subject.

2. Description of Related Art

[0003] Brain injury is common, devastating, and often expensive to treat.

Management of a subject's brain temperature has been recommended by the American Heart Association (AHA) as the standard of care for survivors of cardiac arrest. Brain temperature management also has been used to treat birth-related cerebral damage. Brain temperature management has been studied as a method that reverses and prevents fever after stroke and traumatic brain injury. In addition to its use after brain injury, brain temperature management has been used for more than 50 years to prevent brain injury during cardiac, vascular, and neurological surgery. Brain temperature management is relevant to a variety of central nervous system conditions, including stroke, mechanical brain trauma, and spinal cord injury. A variety of devices have been proposed for therapeutic organ cooling and, in particular, therapeutic cooling of the brain. Such devices generally fall into one of two broad categories: systemic devices and selective devices.

[0004] Systemic devices are widely used today, but limitations, such as systemic toxicity caused by cooling the body core and delays in reaching desired brain temperature, diminish the benefit that subjects may receive. On the other hand, selective cooling enables, for example, the creation of a temperature gradient between the brain and the body core. Selective cooling also can reduce complications associated with body core cooling, improve subject safety, and enable deep cooling of the brain tissue to achieve neuro-protection. [0005] In general, a high degree of selectivity in temperature management has required a high, and generally undesirable, degree of invasiveness. Surgically invasive devices, such as intravascular devices, often focus on cooling the blood supply to a target area and warming the returning blood supply to prevent cooling of the body core. Intravascular systems and other similarly invasive devices, however, may not be suitable for rapid deployment because, for example, they may require intervention by a surgeon. A further limitation of tube-/catheter-based devices is that they require surgical invasion of a major blood vessel, introducing risk of infection, bleeding, thrombosis, rupture of the blood vessel, dissection of the blood vessel wall, and introduction or dislodging debris in the vasculature. These risks are further increased when an intravascular warming catheter is introduced to re-warm blood flow returning from the cooled organ(s).

[0006] Other selective, brain-focused, non-invasive cooling devices require nebulized fluids that undergo a phase change (evaporation) in an attempt to maximize a rate of heat transfer from the body. An example of this method is described, for example, in U.S. Patent No. 7,837,722 to Barbut et al. Drawbacks of this approach include exposure of the subject to fluorocarbon coolant, exposure of bystanders to fluorocarbon coolant, and the formation of entrained debris that is difficult to recapture as the coolant leaves the subject. Also, this approach appears to yield a relatively slow cooling rate in human trials and a shallow average depth of cooling of steady-state reduction in brain temperature.

[0007] Another selective cooling device is described in U.S. Patent No. 7,189,253 to

Lunderqvist et al. The Lunderqvist devices introduce fluid-filled balloons into the nasal cavity and cool the cavity by recirculating cold fluid. These devices affect brain temperature by adjusting the temperature of the cooling fluid based on measurement of tympanic membrane temperature. Drawbacks of this approach include a reduction in heat transfer rate due to a reduction in surface area exploited (e.g., contact with the surface area of the sinuses is not maximized, and air in the sinuses reduces heat transfer) and the heat transfer resistance of the balloon itself.

[0008] Other conventional approaches utilize balloon-based devices, such as those disclosed by Takeda in U.S. Patent Publication Nos. 2008/0086186 and 2009/0177258. Such contained use of fluids generally does not, for example, provide good surface contact with the tissues of the airway, reducing heat transfer. SUMMARY

[0009] This disclosure includes embodiments of cooling devices and methods configured to cool the brain of a subject. Such devices are configurable to be stationary or substantially stationary in some embodiments (e.g., used in hospitals, medical clinics, and any other health care facility), and in other embodiments, the devices of this disclosure can be mobile/transportable (e.g., used at the scene of an accident, used in an ambulance, helicopter, or other vehicle used to provide health care, and the like). Further, methods described in this disclosure can be continuous, intermittent, or a combination thereof, depending on the circumstances. For example, in some instances, a health care provider may implement an intermittent method described in this disclosure to begin cooling the aerodigestive tract of a subject, whether in a health care facility or elsewhere, and then implement a continuous method of cooling the aerodigestive tract of a subject described in this disclosure to continue cooling, whether in a health care facility or elsewhere. In other instances, a health care provider may implement a continuous method described in this disclosure to begin cooling the aerodigestive tract of a subject, whether in a health care facility or elsewhere, and then implement an intermittent method of cooling the aerodigestive tract of a subject described in this disclosure to continue cooling, whether in a health care facility or elsewhere. Such continuous and intermittent methods can be alternated as necessary under the circumstances. Applications of the present devices and methods are relevant to numerous medical procedures and conditions, such as, for example, aneurism coiling/stenting, neurosurgery/neurotrauma surgery, traumatic brain injury, body trauma/exsanguination, surgical exsanguination, birth/maternal exsanguination, atrial ablation, ortho surgery, cardiac surgery, general surgery, cardiac arrest, respiratory arrest, stroke -ischemic, stroke-hemmorhagic, transcatheter aortic valve implantation, full arrest surgery, carcinoembryonic antigen, vascular surgery, birth anoxia, and the like.

[0010] Some embodiments of the present methods for cooling the brain comprise transporting a device to a subject, where the device is configured to introduce free-flowing cooling fluid through a plurality of tubes into the aerodigestive tract of the subject; introducing free-flowing cooling fluid through the plurality of tubes and into the aerodigestive tract of the subject; and continuing to cool the aerodigestive tract of the subject until a brain to body core temperature gradient of at least 1 °C is reached. Some embodiments further comprise transporting the subject to a destination; and continuing to cool the aerodigestive tract of the subject until a brain to body core temperature gradient of at least 1 °C is reached. Some embodiments further comprise transporting the subject and the device to a destination; and continuing to introduce free-flowing cooling fluid through the plurality of tubes of the device into the aerodigestive tract of the subject until brain to body core temperature gradient of at least 1 °C is reached. Some embodiments further comprise reducing blood flow to the subject's brain. In some embodiments, the temperature gradient of at least 1 °C is reached in 30 minutes or less. In some embodiments, the temperature gradient of at least 1 °C is reached in 25 minutes or less. In some embodiments, the temperature gradient of at least 1 °C is reached in 20 minutes or less. In some embodiments, the temperature gradient of at least 1 °C is reached in 15 minutes or less. In some embodiments, the temperature gradient of at least 1 °C is reached in 10 minutes or less. In some embodiments, the temperature gradient of at least 1 °C is reached in 5 minutes or less. In some embodiments, a brain to body core temperature gradient of at least 2 °C is reached. In some embodiments, a brain to body core temperature gradient of at least 3 °C is reached. In some embodiments, a brain to body core temperature gradient of at least 4 °C is reached. In some embodiments, a brain to body core temperature gradient of at least 5 °C is reached. In some embodiments, a brain to body core temperature gradient of at least 6 °C is reached. In some embodiments, a brain to body core temperature gradient of greater than 6 °C is reached. In some embodiments, a brain temperature is measured at the jugular bulb of the subject and is used to determine the brain to body core temperature gradient. Some embodiments further comprise introducing one or more of the plurality of tubes into the nasal cavity of the subject. Some embodiments further comprise introducing one or more of the plurality of tubes into the oral cavity of the subject. Some embodiments further comprise introducing one or more of the plurality of tubes into the nasal cavity of the subject and one or more of the plurality of tubes into the oral cavity of the subject. Some embodiments further comprise positioning one or more of the plurality of tubes exterior to one or more nostrils of the subject such that free-flowing cooling fluid moving through the plurality of tubes can enter the aerodigestive tract of the subject through the one or more nostrils. In some embodiments, one or more of the plurality of tubes is each coupled to a stopper that, if the one or more tubes are positioned exterior to one or more nostrils of the subject, substantially prevents fluid from exiting the one or more nostrils of the subject. Some embodiments further comprise coupling one or more of the plurality of tubes to a mask configured to be positioned over at least one of the nose and the mouth of a subject; and positioning the mask over at least one of the nose and the mouth of the subject such that free- flowing cooling fluid introduced through the one or more of the plurality of tubes can enter the aerodigestive tract of the subject. In some embodiments, at least a portion of the mask is configured to enlarge if in contact with fluid such that fluid is substantially prevented from exiting the mask. In some embodiments, the mask is further configured to facilitate removing fluid from the aerodigestive tract either passively (e.g., with gravity) or actively (e.g., with a suctioning device or vacuum). In some embodiments, where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the methods further comprise introducing cooling boluses into the oral cavity of the subject. In some embodiments, the boluses comprise 100 to 200 milliliters of cooling fluid. In some embodiments, where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the methods further comprise positioning a container containing free-flowing cooling fluid exterior to or interior to one or more nostrils of the subject; and applying pressure to the container such that free-flowing cooling fluid exits the container and is introduced through the one or more nostrils of the subject and into the nasal cavity. In some embodiments, the container is configured to substantially prevent fluid from exiting the one or more nostrils of the subject while free-flowing cooling fluid is being introduced into the nasal cavity of the subject. In some embodiments, where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the methods further comprise introducing a solid-phase coolant into the oral cavity of the subject. In some embodiments, the solid-phase coolant comprises at least one of saline, ice chips, and ice chips in a base of propylene glycol. In some embodiments, where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the methods further comprise introducing at least one of an emulsion and a slurry into the oral cavity of the subject. In some embodiments, where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the methods further comprise positioning a container containing free-flowing cooling fluid exterior to or interior to the mouth of the subject; and applying pressure to the container such that free-flowing cooling fluid exits the container and is introduced into the oral cavity of the subject. Some embodiments further comprise disposing an esophageal blockage in the oral cavity such that fluid is at least partially prevented from entering the stomach of the subject. In some embodiments, the esophageal blockage extends at least to the upper esophageal sphincter. In some embodiments, the esophageal blockage extends at least partially into the stomach and blocks the distal side of the upper esophageal sphincter. In some embodiments, the esophageal blockage is configured to enlarge if in contact with fluid. In some embodiments, the esophageal blockage is compressible such that, if disposed in the esophagus, the esophageal blockage substantially conforms to the shape of the esophagus. In some embodiments, the esophageal blockage comprises a first end and a second end that are in fluid communication. In some embodiments, the esophageal blockage permits introduction of free-flowing cooling fluid near at least one of the oropharynx and hypopharynx. Some embodiments further comprise placing the subject on a board, where the board is configured to position at least a portion of the subject's ears lower than the subject's back. Some embodiments further comprise placing the subject on a board, where the board is configured to position the subject's pharynx lower than the subject's trachea. Some embodiments further comprise positioning the subject's head in a catchment to enable fluid exiting at least one of the nose and the mouth of the subject to be collected in the catchment; removing fluid from the catchment through an opening in the catchment. In some embodiments, the subject's neck is placed in contact with a portion of the catchment to elevate the subject's neck. Some embodiments further comprise adjusting the subject's carbon dioxide partial pressure (pC0₂) level to decrease cerebral blood flow. Some embodiments further comprise reducing the subject's carbon dioxide partial pressure (pC0₂) level to decrease cerebral blood flow. In some embodiments, the free-flowing cooling fluid is cooled by an external device. In some embodiments, the free-flowing cooling fluid is cooled by a chemical reaction or an absorptive process.

[0011] Some embodiments of the present methods further comprise transporting a device to a subject, where the device is configured to introduce free-flowing cooling fluid through a plurality of tubes into the aerodigestive tract of the subject; introducing free- flowing cooling fluid through the plurality of tubes and into the aerodigestive tract of the subject; and continuing to cool the aerodigestive tract of the subject until a target brain to body core temperature gradient is reached in 30 minutes or less. Some embodiments further comprise transporting the subject to a destination; and continuing to cool the aerodigestive tract of the subject until a target brain to body core temperature gradient is reached in 30 minutes or less. Some embodiments further comprise transporting the subject and the device to a destination; and continuing to introduce free-flowing cooling fluid through the plurality of tubes of the device into the aerodigestive tract of the subject until a target brain to body core temperature gradient is reached in 30 minutes or less. Some embodiments further comprise reducing blood flow to the subject's brain. In some embodiments, the target brain to body core temperature gradient is reached in 25 minutes or less. In some embodiments, the target brain to body core temperature gradient is reached in 20 minutes or less. In some embodiments, the target brain to body core temperature gradient is reached in 15 minutes or less. In some embodiments, the target brain to body core temperature gradient is reached is reached in 10 minutes or less. In some embodiments, the target brain to body core temperature gradient is reached in 5 minutes or less. In some embodiments, the target brain to body core temperature gradient is at least 1 °C. In some embodiments, the target brain to body core temperature gradient is at least 2 °C. In some embodiments, the target brain to body core temperature gradient is at least 3 °C. In some embodiments, the target brain to body core temperature gradient is at least 4 °C. In some embodiments, the target brain to body core temperature gradient is at least 5 °C. In some embodiments, the target brain to body core temperature gradient is at least 6 °C. In some embodiments, the target brain to body core temperature gradient is greater than 6 °C. In some embodiments, a brain temperature is measured at the jugular bulb of the subject and is used to determine the brain to body core temperature gradient. Some embodiments further comprise introducing one or more of the plurality of tubes into the nasal cavity of the subject. Some embodiments further comprise introducing one or more of the plurality of tubes into the oral cavity of the subject. Some embodiments further comprise introducing one or more of the plurality of tubes into the nasal cavity of the subject and one or more of the plurality of tubes into the oral cavity of the subject. Some embodiments further comprise positioning one or more of the plurality of tubes exterior to one or more nostrils of the subject such that free-flowing cooling fluid moving through the plurality of tubes can enter the aerodigestive tract of the subject through the one or more nostrils. In some embodiments, one or more of the plurality of tubes is each coupled to a stopper that, if the one or more tubes are positioned exterior to one or more nostrils of the subject, substantially prevents fluid from exiting the one or more nostrils of the subject. Some embodiments further comprise coupling one or more of the plurality of tubes to a mask configured to be positioned over at least one of the nose and the mouth of a subject; and positioning the mask over at least one of the nose and the mouth of the subject such that free-flowing cooling fluid introduced through the one or more of the plurality of tubes can enter the aerodigestive tract of the subject. In some embodiments, at least a portion of the mask is configured to enlarge if in contact with fluid such that fluid is substantially prevented from exiting the mask. In some embodiments, the mask is further configured to facilitate removing fluid from the aerodigestive tract either passively (e.g., with gravity) or actively (e.g., with a suctioning device or vacuum). In some embodiments, where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the methods further comprise introducing cooling boluses into the oral cavity of the subject. In some embodiments, the boluses comprise 100 to 200 milliliters of cooling fluid. In some embodiments, where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the methods further comprise positioning a container containing free- flowing cooling fluid exterior to or interior to one or more nostrils of the subject; and applying pressure to the container such that free-flowing cooling fluid exits the container and is introduced through the one or more nostrils of the subject and into the nasal cavity. In some embodiments, the container is configured to substantially prevent fluid from exiting the one or more nostrils of the subject while free-flowing cooling fluid is being introduced into the nasal cavity of the subject. In some embodiments, where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the methods further comprise introducing a solid-phase coolant into the oral cavity of the subject. In some embodiments, the solid-phase coolant comprises at least one of saline, ice chips, and ice chips in a base of propylene glycol. In some embodiments, where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the methods further comprise introducing at least one of an emulsion and a slurry into the oral cavity of the subject. In some embodiments, where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the methods further comprise positioning a container containing free-flowing cooling fluid exterior to or interior to the mouth of the subject; and applying pressure to the container such that free-flowing cooling fluid exits the container and is introduced into the oral cavity of the subject. Some embodiments further comprise disposing an esophageal blockage in the oral cavity such that fluid is at least partially prevented from entering the stomach of the subject. In some embodiments, the esophageal blockage extends at least to the upper esophageal sphincter. In some embodiments, the esophageal blockage extends at least partially into the stomach and blocks the distal side of the upper esophageal sphincter. In some embodiments, the esophageal blockage is configured to enlarge if in contact with fluid. In some embodiments, the esophageal blockage is compressible such that, if disposed in the esophagus, the esophageal blockage substantially conforms to the shape of the esophagus. In some embodiments, the esophageal blockage comprises a first end and a second end that are in fluid communication. In some embodiments, the esophageal blockage permits introduction of free-flowing cooling fluid near at least one of the oropharynx and hypopharynx. Some embodiments further comprise placing the subject on a board, where the board is configured to position at least a portion of the subject's ears lower than the subject's back. Some embodiments further comprise placing the subject on a board, where the board is configured to position the subject's pharynx lower than the subject's trachea. Some embodiments further comprise positioning the subject's head in a catchment to enable fluid exiting at least one of the nose and the mouth of the subject to be collected in the catchment; removing fluid from the catchment through an opening in the catchment. In some embodiments, the subject's neck is placed in contact with a portion of the catchment to elevate the subject's neck. Some embodiments further comprise adjusting the subject's carbon dioxide partial pressure (pC0₂) level to decrease cerebral blood flow. Some embodiments further comprise reducing the subject's carbon dioxide partial pressure (pC0₂) level to decrease cerebral blood flow. In some embodiments, the free-flowing cooling fluid is cooled by an external device. In some embodiments, the free-flowing cooling fluid is cooled by a chemical reaction or an absorptive process.

[0012] Some embodiments of the present device comprise an power source; a pump coupled to the power source; a plurality of tubes coupled to a fluid source; where the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a brain to body core temperature gradient of at least 1 °C is reached. Some embodiments of the present devices comprise a power source; a pump coupled to the power source; a plurality of tubes coupled to a fluid source; where the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a target brain to body core temperature gradient is reached in 30 minutes or less. Some embodiments further comprise a catchment positionable to enable fluid exiting at least one of the nose and the mouth of the subject to be collected in the catchment, the catchment coupled to the pump with an exit tube; where the pump is configured, if activated, to enable fluid to be pumped from the catchment. Some embodiments further comprise pinch clamps coupled to one or more of the plurality of tubes to enable flow through the one or more of the plurality of tubes to be adjusted. In some embodiments, at least one of a positive pressure or a hydrostatic pressure enables free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of the subject. Some embodiments further comprise a heat exchanger. In some embodiments, the heat exchanger is the fluid source. Some embodiments further comprise a second pump; and a catchment positionable to enable fluid exiting at least one of the nose and the mouth of the subject to be collected in the catchment, the catchment coupled to an exit tube; where the first pump and the second pump are each configured, if activated, to enable free-flowing cooling fluid to be pumped through one or more of the plurality of tubes and into the aerodigestive tract of a subject. Some embodiments further comprise a third pump, where the third pump is configured, if activated, to enable free-flowing cooling fluid to be removed from the catchment. In some embodiments, the third pump is a vacuum. In some embodiments, a flow rate of each of the first pump, the second pump, and the third pump can be adjusted independently. Some embodiments further comprise one or more filters; and one or more heat exchangers coupled to the one or more filters; where fluid exiting the catchment passes through the one or more filters and subsequently passes through the one or more heat exchangers. Some embodiments further comprise one or more filters; and one or more heat exchangers coupled to the one or more filters; where fluid exiting the catchment passes through the one or more heat exchangers and subsequently passes through the one or more filters. In some embodiments, the fluid source is under a vacuum. In some embodiments, one or more of the heat exchangers is electrically isolated. Some embodiments further comprise one or more pressure monitors configured to measure pressure of free- flowing cooling fluid in one or more of the plurality of tubes. In some embodiments, the one or more heat exchangers are the fluid source. In some embodiments, one or more pumps is a double-headed pump, a roller pump, or a centrifugal pump. In some embodiments, the power source comprises manual power. In some embodiments, the power source comprises chemical power. In some embodiments, the device comprises an outlet plug that enables the device to be coupled to a secondary power source. In some embodiments, the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a brain to body core temperature gradient of at least 2 °C is reached. In some embodiments, the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a brain to body core temperature gradient of at least 3 °C is reached. In some embodiments, the device is configured, if activated, to enable free- flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a brain to body core temperature gradient of at least 4 °C is reached. In some embodiments, the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a brain to body core temperature gradient of at least 5 °C is reached. In some embodiments, the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a brain to body core temperature gradient of at least 6 °C is reached. In some embodiments, the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a brain to body core temperature gradient of greater than 6 °C is reached. In some embodiments, the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a target brain to body core temperature gradient is reached in 25 minutes or less. In some embodiments, the device is configured, if activated, to enable free- flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a target brain to body core temperature gradient is reached in 20 minutes or less. In some embodiments, the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a target brain to body core temperature gradient is reached in 15 minutes or less. In some embodiments, the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a target brain to body core temperature gradient is reached in 10 minutes or less. In some embodiments, the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a target brain to body core temperature gradient is reached in 5 minutes or less. In some embodiments, the device is configured to enable blood flow to the subject's brain to be reduced. In some embodiments, a brain temperature is measured at the jugular bulb of the subject and is used to determine the brain to body core temperature gradient. In some embodiments, one or more of the plurality of tubes are configured to be introduced into the nasal cavity of the subject. In some embodiments, one or more of the plurality of tubes are configured to be introduced into the oral cavity of the subject. In some embodiments, one or more of the plurality of tubes are configured to be introduced into the nasal cavity of the subject, and one or more of the plurality of tubes is configured to be introduced into the oral cavity of the subject. In some embodiments, one or more of the of the plurality of tubes are configured to be positioned exterior to one or more nostrils of the subject such that free- flowing cooling fluid moving through the plurality of tubes can enter the aerodigestive tract of the subject through the one or more nostrils. Some embodiments further comprise a stopper coupled to at least one of the one or more tubes such that, if the one or more tubes are positioned exterior to one or more nostrils of the subject, the stopper substantially prevents fluid from exiting the one or more nostrils of the subject. Some embodiments further comprise a mask coupled to one or more of the plurality of tubes, the mask configured to be positioned over at least one of the nose and the mouth of a subject such that free-flowing cooling fluid introduced through the one or more of the plurality of tubes can enter the aerodigestive tract of the subject. In some embodiments, at least a portion of the mask is configured to enlarge if in contact with fluid such that fluid is substantially prevented from exiting the mask. In some embodiments, the mask is further configured to facilitate removing fluid from the aerodigestive tract either passively (e.g., with gravity) or actively (e.g., with a suctioning device or vacuum). Some embodiments further comprise an esophageal blockage configured to be disposed in the oral cavity such that fluid is at least partially prevented from entering the stomach of the subject. In some embodiments, the esophageal blockage extends at least to the upper esophageal sphincter. In some embodiments, the esophageal blockage extends at least partially into the stomach and blocks the distal side of the upper esophageal sphincter. In some embodiments, the esophageal blockage is configured to enlarge if in contact with fluid. In some embodiments, the esophageal blockage is compressible such that, if disposed in the esophagus, the esophageal blockage substantially conforms to the shape of the esophagus. In some embodiments, the esophageal blockage comprises a first end and a second end that are in fluid communication. In some embodiments, the esophageal blockage permits introduction of free-flowing cooling fluid near at least one of the oropharynx and hypopharynx. Some embodiments further comprise a board configured to position at least a portion of the subject's ears lower than the subject's back. Some embodiments further comprise a board configured to position the subject's pharynx lower than the subject's trachea. Some embodiments further comprise a catchment configured to enable fluid exiting at least one of the nose and the mouth of the subject to be collected in the catchment, the catchment comprising an opening through which fluid in the catchment can exit. In some embodiments, the catchment is configured to elevate the subject's neck. In some embodiments, the free-flowing cooling fluid is cooled by an external device. In some embodiments, the free-flowing cooling fluid is cooled by a chemical reaction or an absorptive process. In some embodiments, the pump is configured, if activated, to enable free-flowing cooling fluid to be pumped through one or more of the plurality of tubes and into the aerodigestive tract of a subject and to enable fluid to be pumped from the catchment. In some embodiments, the power source is an independent power source.

[0013] Some embodiments of the present methods comprise positioning the subject's pharynx lower than the subject's trachea. In some embodiments, cooling fluid is introduced and removed from the subject's aerodigestive tract at a rate that prevents the cooling fluid from flowing in to the subject's trachea. In some embodiments, the cooling fluid is delivered and removed through a plurality of tubes. In some embodiments, the volume of cooling fluid in the subject's aerodigestive tract is controlled such that an esophageal blockage or balloon is not required. In some embodiments, the volume of cooling fluid in the subject's aerodigestive tract is controlled such that a balloon preventing fluid flow into the trachea is not required. In some embodiments, no tracheal intubation is required. In some embodiments, the positioning the subject's pharynx lower than the subject's trachea comprises placing the subject on a board where the relative position of the subject's pharynx to the subject's trachea is adjusted by moving the board.

[0014] Any embodiment of any of the present cooling devices and methods can consist of or consist essentially of - rather than comprise/include/contain/have - any of the described elements and/or features. Thus, in any of the claims, the term "consisting of or "consisting essentially of can be substituted for any of the open-ended linking verbs recited above, in order to change the scope of a given claim from what it would otherwise be using the open-ended linking verb.

[0015] The term "aerodigestive tract" refers to a complex of organs that, in total, make up the tissues and organs of the upper respiratory tract and the upper part of the digestive tract. The aerodigestive tract, as used herein, can include the lips and mouth, tongue, nose, throat, vocal cords, esophagus, stomach and/or trachea. The aerodigestive tract does not include the lungs. The phrase "introducing liquid into the aerodigestive tract" includes introducing liquids into any part of the aerodigestive tract, such as the nasal cavity, upper airway (nasal and oral cavity and pharynx), the nasal cavity and upper airway and esophagus, or the nasal cavity and upper airway and esophagus and stomach, or any combination or sub-combination thereof.

[0016] The term "coupled" is defined as connected, although not necessarily directly, and not necessarily mechanically. Two items are "couplable" if they can be coupled to each other. Unless the context explicitly requires otherwise, items that are couplable are also decouplable, and vice-versa. One non-limiting way in which a first structure is couplable to a second structure is for the first structure to be configured to be coupled (or configured to be couplable) to the second structure.

[0017] The terms "a" and "an" are defined as one or more unless this disclosure explicitly requires otherwise.

[0018] The term "substantially" is defined as largely but not necessarily wholly what is specified (and includes what is specified; e.g., substantially 90 degrees includes 90 degrees and substantially parallel includes parallel), as understood by a person of ordinary skill in the art. In any disclosed embodiment, the terms "substantially," "approximately," and "about" may be substituted with "within [a percentage] of what is specified, where the percentage includes 0.1, 1, 5, and 10 percent.

[0019] The terms "comprise" (and any form of comprise, such as "comprises" and

"comprising"), "have" (and any form of have, such as "has" and "having"), "include" (and any form of include, such as "includes" and "including") and "contain" (and any form of contain, such as "contains" and "containing") are open-ended linking verbs. As a result, a cooling device, or a component of a cooling device, that "comprises," "has," "includes" or "contains" one or more elements or features possesses those one or more elements or features, but is not limited to possessing only those elements or features. Likewise, a cooling method that "comprises," "has," "includes" or "contains" one or more steps possesses those one or more steps, but is not limited to possessing only those one or more steps. Additionally, terms such as "first" and "second" are used only to differentiate structures or features, and not to limit the different structures or features to a particular order.

[0020] The feature or features of one embodiment may be applied to other embodiments, even though not described or illustrated, unless expressly prohibited by this disclosure or the nature of the embodiments.

[0021] Details associated with the embodiments described above and others are presented below.

BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The following drawings illustrate by way of example and not limitation. For the sake of brevity and clarity, every feature of a given structure is not always labeled in every figure in which that structure appears. Identical reference numbers do not necessarily indicate an identical structure. Rather, the same reference number may be used to indicate a similar feature or a feature with similar functionality, as may non-identical reference numbers. Some of the figures illustrate some of the described elements using graphical symbols that will be understood by those of ordinary skill in the art.

[0023] FIGS. 1-12 depict various embodiments of the present cooling devices that are each configured to enable free-flowing cooling fluid to pass through a plurality of tubes and into the aerodigestive tract of a subject.

[0024] FIG. 13 depicts one embodiment of a board on which a subject can be positioned while cooling the aerodigestive tract of the subject.

[0025] FIGS. 14-15 depict embodiments of a catchment on which a subject can be positioned while cooling the aerodigestive tract of the subject.

[0026] FIGS. 16-18 depict theoretical examples of cooling power that can be achieved with a given mass of a given material.

DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

[0027] Embodiments of cooling devices and methods are disclosed in U.S. Patent No.

8,308,787, filed July 23, 2010 ("the '787 Patent"), U.S. Patent Application No. 13/558,108, filed July 25, 2012 ("the Ί08 Application"), U.S. Patent Application No. 13/674,701, filed November 12, 2012 ("the '701 Application"), International Application No. PCT/US 14/43509 ("the '509 International Application"), filed June 20, 2014, and United States Provisional Patent Application No. 61/949,411 ("the '411 Provisional Application"), filed March 7, 2014, each of which is incorporated by reference in its entirety.

[0028] A pump described in this disclosure or depicted with graphical symbols in the figures can be any device configured to move fluid, for example, through one or more tubes (e.g., catheters) coupled to the device, whether through positive or negative pressure, such as a roller pump, a centrifugal pump, a double-headed pump, a vacuum, and the like. The term can be used to describe a device that introduces fluid into the body of a subject or a device that removes fluid from the body of a subject. The term can be used to describe a single device or a plurality of devices. For example, if a plurality of tubes of the present cooling devices are coupled to a pump, each of the plurality of tubes can be coupled to an independent pump or can share a pump with one or more of the plurality of tubes. For example, in some embodiments, it may be advantageous to have each of a plurality of tubes coupled to a separate pump to, for example, increase the ability to monitor/adjust the amount of fluid moving through each tube, to monitor/adjust the pressure at any point along each tube, and/or to monitor/address differences in resistance to flow inside the aerodigestive tract of a subject that may affect a desired fluid distribution through the tubes or in the aerodigestive tract. Further, a pump can be manually operated (e.g., by rotating or reciprocating a pump handle, by depressing the plunger (e.g., of a syringe), and the like) or non-manually operated (e.g., by actuating an electrically operated pump). Any pump in an embodiment that comprises a plurality of pumps can comprise (or be configured to comprise) the same flow rate or a different flow rate than other pumps in the plurality of pumps. A pump of the present disclosure can include any pump (and any component of any pump) disclosed in the '787 Patent, the Ί08 Application, the '701 Application, the '509 International Application, and the '411 Provisional Application. Further, the present disclosure includes any components configured to be coupled to and/or integrated with a pump that are disclosed in the '787 Patent, the ' 108 Application, the '701 Application, the '509 International Application, and the '411 Provisional Application, such as tubes, heat exchangers, controllers, and the like.

[0029] In the present devices and methods, fluid can be introduced into the aerodigestive tract of a subject with one or more tubes. A tube exterior to a nostril or inserted into the nares or the nasal cavity can, for example, be directed toward the cranial region of the nasal cavity such that, if activated, the present devices can introduce fluid into the aerodigestive tract of a subject. Similarly, tubes exterior to the mouth or inserted into mouth or the oral cavity can, for example, be directed into the aerodigestive tract such that, if activated, the present devices can introduce fluid into the aerodigestive tract of a subject. As with any of the tubes in this disclosure, tubes can also be used to remove fluid from the aerodigestive tract of a subject. Embodiments configured to remove fluid from the aerodigestive tract can assist in improving heat exchange between fluid and tissue in the aerodigestive tract (e.g., by removing air that prevents optimal distribution of fluid on mucosal surfaces, or by removing fluid that is not sufficiently cool). Air can also be removed by temporary interruption of fluid flow (e.g., which can allow air to rise in a tube) in combination with temporary interruption of any seal (e.g., in the peri-nares area), which allows air to escape into the environment. A tube of the present disclosure can comprise one opening or more than one opening through which fluid can exit the tube. Further, a tube of the present disclosure can comprise one lumen or more than one lumen (e.g., such that fluid can be passed through multiple lumens of the same tube to, for example, introduce fluid into the aerodigestive tract, remove fluid from the aerodigestive tract, inflate a blockage, deflate a blockage, and combinations thereof). A tube in this disclosure can comprise any suitable, biocompatible material. Such materials can be malleable, rigid, or a combination thereof. In some embodiments, a tube can comprise a friction-reducing coating, such as Teflon, to enable the tube to be more easily inserted into a region of the aerodigestive tract of a subject.

[0030] As described in detail in the '787 Patent, the Ί08 Application, the '701

Application, the '509 International Application, and the '411 Provisional Application, fluid used by the present devices and in the present methods can include any free-flowing (e.g., non-nebulized) fluid, such as perfluorocarbons, water, and/or oil, and combinations thereof, each of which can further comprise additives, such as simple sugars, organic compounds (e.g., propylene glycol), antibacterial agents, mucosal protectants (e.g., antioxidants, free- radical scavengers, etc.), and/or electrolytes (e.g., potassium, calcium, sodium, and the like). Further, fluid used by the present devices and in the present methods is generally cooled fluid that can range in temperature, for example, from 30 °C to -30 °C; however, in some embodiments, the fluid can be greater than 30 °C or less than -30 °C. In some embodiments, fluid can passively flow out of the nose and/or mouth of the subject; and in other embodiments, fluid is actively removed from the nose and/or mouth of the subject (e.g., with a suctioning device), as will be discussed further. [0031] The present devices and methods enable a brain to body core temperature gradient to be reached by introducing fluid, generally free-flowing, cooled fluid, into the aerodigestive tract of a subject. In some embodiments, a brain to body temperature gradient of at least 1 °C is reached (e.g., a temperature gradient of 1 °C, 2 °C, 3 °C, 4 °C, 5 °C, 6 °C, 7 °C, 8 °C, 9 °C, 10 °C, or more); however, in other embodiments, a brain to body temperature gradient of less than 1 °C is reached while accomplishing some or all objectives relating to a given subject. In some embodiments, the present devices and methods enable the brain of a subject to be cooled for a target duration of time, such as for at least 5 minutes (e.g., 5 minutes, 10 minutes, 15, minutes, 20 minutes, 25 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hour, or more). In some embodiments, the present devices and methods enable the brain of a subject to be cooled to a brain to body core temperature gradient of at least 1 °C is in a target duration of time, such as in 30 minutes or less (e.g., 30 minutes, 25 minutes, 20 minutes, 15 minutes, 10 minutes, 5 minutes, or less). In some embodiments, the present devices and methods enable a target brain to body core temperature gradient, such as any of those described above, to be reached in a target duration of time, such as any of those described in above. In some embodiments, the present devices and methods enable the brain to be cooled with a target volume of fluid, such at least 100 milliliters of fluid (e.g., 100 milliliters, 150 milliliters, 200 milliliters, 250 milliliters, 500 milliliters, 750 milliliters, 1 liter, 1.25 liters, 1.5 liters, 1.75 liters, 2 liters, or more).

[0032] In some embodiments, the devices of this disclosure (or components thereof) can be coupled or couplable (directly or indirectly) to an independent power source (e.g., a power source that provides power without being coupled to an electrical grid), such as, for example, a manual power source (e.g., rotating or reciprocating a handle, by depressing or extending a plunger, and the like), a chemical power source, a solar power source, and/or a standalone electrical power source; and, in other embodiments, the devices of this disclosure (or components thereof) can be coupled or couplable (directly or indirectly) to a dependent power source (e.g., an electrical grid), such as with an outlet plug. In some embodiments, the primary power source of the devices of this disclosure (or components thereof) is an independent power source, and the devices (or components thereof) can be coupled or couplable (directly or indirectly) to a dependent power source as a secondary power source; and, in other embodiments, the primary power source of the devices of this disclosure (or components thereof) is a dependent power source, and the devices (or components thereof) can be coupled or couplable (directly or indirectly) to an independent power source. [0033] FIG. 1 depicts one embodiment of the present devices 100a. Device 100a comprises pumps 104a, 108a, and 112a. Pumps 104a, 108a, and 112a (or components thereof) can be fluidically isolated from fluid in device 100a (e.g., a roller pump, as depicted in FIG. 1) or can be in fluid communication with fluid in device 100a (e.g., a centrifugal pump (e.g., with a disposable head section), as depicted in FIG. 2, a diaphragm pump (e.g., with a disposable diaphragm section), and the like). In the embodiment shown, pump 104a is coupled to tube 116a and 120a by a Y-fitting that directs fluid from pump 104a into tubes 116a and 120a. In some embodiments, tubes 116a and 120a are each coupled directly to pump 104a. Tubes 116a and 120a are coupled to fluid source 124a via pump 104a such that, if activated, pump 104a can pump fluid from fluid source 124a through tubes 116a and 120a and into the aerodigestive tract of a subject (e.g., into the nasal cavity). Pump 108a is coupled to tube 128a. Tube 128a is coupled to fluid source 124a via pump 108a such that, if activated, pump 108a can pump fluid from fluid source 124a through tube 128a and into the aerodigestive tract of a subject (e.g., into the oral cavity and/or esophagus). In some embodiments, device 100a is configured such that a positive pressure head is applied to the pump inlets, such as by positioning fluid source 124a higher than the pumps and/or by applying a positive pressure to fluid source 124a. If device 100a is activated, device 100a is configured to enable free-flowing cooling fluid (e.g., from fluid source 124a) to pass through tubes 116a, 120a, and/or 128a and into the aerodigestive tract of a subject until a brain to body core temperature gradient of at least 1 °C is reached and/or until a target brain to body core temperature gradient is reached in 30 minutes or less, or both.

[0034] In the embodiment shown, pump 112a is coupled to catchment 132a by exit tube 136a. Fluid can exit catchment 132a as a result of positive pressure (e.g., hydrostatic pressure), negative pressure (e.g., pump 112a), or both. Catchment 132a can be positionable (e.g., about a subject's head) to enable fluid exiting the nose and/or the mouth of the subject to be collected in the catchment. In some embodiments, 132a comprises an active return. In some embodiments, the active return comprises a mask coupled to a tube or a plurality of tubes. In some embodiments, the active return comprises a tube or a plurality of tubes that are inserted into the mouth of the subject. In the embodiment shown, pump 112a is configured, if activated, to enable fluid to be pumped from catchment 132a through filter 140a and through heat exchanger 144a, which is coupled to chiller 148a such that chiller 148a can cool fluid passing through heat exchanger 144a, and into fluid source 124a. In such an embodiment, where heat exchanger 144a and chiller 148a are disposed downstream from filter 140a, any fluid that is frozen in heat exchanger 144a can flow into fluid source 124a, rather than being filtered, in order to increase cooling of the free-flowing fluid. In each of the embodiments disclosed and depicted, the term chiller is used to describe any cold source, which can be achieved with various devices, including, for example, electrical, mechanical, and chemical. Chillers may also include a heat source coupled to a temperature controller. In some embodiments a chiller with a cold source and heat source may downregulate and upregulate the temperature of the free flowing fluid. Heat exchangers and chillers can be integral, such they form two components of the same device, or coupled to one another such that they are two separate devices. Device 100a further comprises pressure monitor 152a, which is configured to measure pressure of fluid prior to the fluid entering tubes 116a and 120a, and pressure monitor 154a, which is configured to measure pressure of fluid in tube 128a. As explained above, device 100a (or components thereof, such as one or more pumps) can be coupled to or couplable to a dependent and/or independent power source.

[0035] FIG. 2 depicts another embodiment of the present devices 100b. Device 100b of FIG. 2 comprises a similar configuration to device 100a of FIG. 1, and the components of device 100b depicted in FIG. 2 can comprise the same or similar functions and characteristics as components depicted and described with respect to device 100a of FIG. 1. FIG. 2 demonstrates that a variety of types of pumps can be used in the present devices and methods, such as pumps, at least a portion of which, are fluidically isolated from fluid passing through device 100b (e.g., a roller pump).

[0036] FIG. 3 depicts another embodiment of the present devices 100c. Device 100c of FIG. 3 comprises a similar configuration to device 100a of FIG. 1, and the components of device 100c depicted in FIG. 3 can comprise the same or similar functions and characteristics as components depicted and described with respect to device 100a of FIG. 1. Further, FIG. 3 depicts a configuration in which heat exchange is electrically isolated from some or all of the other components of device 100c, such as by circulating non-conductive fluid (e.g., oil) between heat exchanger 144c and heat exchanger 145 c (which is electrically isolated, in the embodiment shown), and by circulating conductive fluid (e.g., glycol) between heat exchanger 145c and chiller 148c.

[0037] FIG. 4 depicts another embodiment of the present devices lOOd. Device lOOd of FIG. 4 comprises a similar configuration to device 100a of FIG. 1, and the components of device lOOd depicted in FIG. 4 can comprise the same or similar functions and characteristics as components depicted and described with respect to device 100a of FIG. 1. Further, FIG. 4 depicts fluid source 124d coupled to pumps 104d and 108d by a tube with a Y-fitting that directs fluid from fluid source 124d into tubes 116a and 120a. [0038] FIG. 5 depicts another embodiment of the present devices lOOe. Device lOOe comprises pumps 104e and 108e. Pumps 104e and 108e (or components thereof) can be fluidically isolated from fluid in device lOOe (e.g., a roller pump) or can be in fluid communication with fluid in device lOOe (e.g., a centrifugal pump (e.g., with a disposable head section), a diaphragm pump (e.g., with a disposable diaphragm section), and the like). In the embodiment shown, pump 104e is coupled to tube 116e and 120e by a Y-fitting that directs fluid from pump 104e into tubes 116e and 120e. In some embodiments, tubes 116e and 120e are each coupled directly to pump 104e. Tubes 116e and 120e are coupled to fluid source 124e via pump 104e such that, if activated, pump 104e can pump fluid from fluid source 124e through tubes 116e and 120e and into the aerodigestive tract of a subject (e.g., into the nasal cavity). Pump 108e is coupled to tube 128e. Tube 128e is coupled to fluid source 124e via pump 108e such that, if activated, pump 108e can pump fluid from fluid source 124e through tube 128e and into the aerodigestive tract of a subject (e.g., into the oral cavity). In the embodiment shown, fluid source 124e is under negative pressure via vacuum 125e, which is regulated by regulator 126e, and fluid inadvertently removed through vacuum lines can be collected in trap 127e. If device lOOe is activated, device lOOe is configured to enable free-flowing cooling fluid (e.g., from fluid source 124e) to pass through tubes 116e, 120e, and/or 128e and into the aerodigestive tract of a subject until a brain to body core temperature gradient of at least 1 °C is reached and/or until a target brain to body core temperature gradient is reached in 30 minutes or less, or both.

[0039] In the embodiment shown, device lOOe comprises catchment 132e, which is positionable (e.g., about a subject's head) to enable fluid exiting the nose and/or the mouth of the subject to be collected in the catchment. Catchment 132e is coupled to exit tube 136e. Fluid in catchment 132e can exit catchment 132e as a result of positive pressure (e.g., hydrostatic), negative pressure (e.g., vacuum 125e), or both. In the embodiment shown, device lOOe enables fluid to pass from catchment 132e into fluid source 124e by hydrostatic pressure and/or by vacuum 125e, if activated. In some embodiments, 132e comprises an active return. In some embodiments, the active return comprises a mask coupled to a tube or a plurality of tubes. In some embodiments, the active return comprises a tube or a plurality of tubes that are inserted into the mouth of the subject. Pumps 104e and 108e and vacuum 125e enable fluid to pass from fluid source 124e into tubes 116e, 120e and 128e, via filters 140e and 142e. Heat exchangers 144e, 145e and 146e (both of heat exchangers 145e and 146e are electrically isolated, in the embodiment shown), and chillers 148e and 149e are upstream from filters 140e and 142e. In the embodiment shown, heat exchange is electrically isolated from some or all of the other components of device lOOe, such as by circulating non- conductive fluid (e.g., oil) between heat exchangers 144e, 145e, 146e (e.g., using oil pump 147e), and circulating conductive fiuid (e.g., glycol) between heat exchanger 145e and chiller 148e and between heat exchanger 146e and chiller 149e, such that heat exchanger 144e can cool fluid from fluid source 124e prior to entering tubes 116e, 120e, and 128e. However, as in embodiments described above, heat exchange is not required to be electrically isolated in device lOOe. Purge lines depicted between filters 140e and 142e prevent accumulation of air in filters 140e and 142e. Though not depicted, such purge lines can be used in any of the configurations described throughout this disclosure. Device lOOe further comprises pressure monitor 152e, which is configured to measure pressure of fluid passing through filter 140e, and pressure monitor 154e, which is configured to measure pressure of fluid passing through filter 142e. As explained above, device lOOe (or components thereof, such as one or more pumps) can be coupled to or couplable to a dependent and/or independent power source.

[0040] FIG. 6 depicts another embodiment of the present devices lOOf. Device lOOf of FIG. 6 comprises a similar configuration to device lOOe of FIG. 5, and the components of device lOOf depicted in FIG. 6 can comprise the same or similar functions and characteristics as components depicted and described with respect to device lOOe of FIG. 5. FIG. 6 depicts an embodiment of the present devices in which heat exchange is not electrically isolated, and conductive fluid (e.g., glycol) is circulated between heat exchanger 144f and chiller 148f to cool fluid from fiuid source 124f by passing the fluid through heat exchanger 144f prior to entering tubes 116f, 120f, and 128f.

[0041] FIG. 7 depicts another embodiment of the present devices lOOg. Device lOOg of FIG. 7 comprises a similar configuration to device lOOe of FIG. 5, and the components of device lOOg depicted in FIG. 7 can comprise the same or similar functions and characteristics as components depicted and described with respect to device lOOe of FIG. 5. FIG. 7 depicts an embodiment of the present devices in which fluid in catchment 132f can exit catchment 132f as a result of hydrostatic pressure and without a pump. In some embodiments, 132f comprises an active return. In some embodiments, the active return comprises a mask coupled to a tube or a plurality of tubes. In some embodiments, the active return comprises a tube or a plurality of tubes that are inserted into the mouth of the subject.

[0042] FIG. 8 depicts another embodiment of the present devices lOOh. Device lOOh of FIG. 8 comprises a similar configuration to device lOOe of FIG. 5, and the components of device lOOh depicted in FIG. 8 can comprise the same or similar functions and characteristics as components depicted and described with respect to device lOOe of FIG. 5. FIG. 8 demonstrates that a variety of types of pumps can be used in the present devices and methods, such as pumps that, at least a portion of which, are in fluidic contact with fluid passing through device lOOh.

[0043] FIG. 9 depicts another embodiment of the present devices lOOi. Device lOOi comprises pump 104i. Pump 104i (or components thereof) can be fluidically isolated from fluid in device lOOi (e.g., a roller pump) or can be in fluid communication with fluid in device lOOi (e.g., a centrifugal pump (e.g., with a disposable head section), a diaphragm pump (e.g., with a disposable diaphragm section), and the like). Device lOOi further comprises tubes 116i and 120i coupled to fluid source 124i by a Y-fitting that directs fluid from fluid source 124i into tubes 116i and 120i. In some embodiments, tubes 116i and 120i are each coupled directly to fluid source 124i. Device lOOi further comprises tube 128i coupled to fluid source 124i. Tubes 116i, 120i, and 128i are coupled to fluid source 124i such that positive pressure, such as hydrostatic pressure (e.g., by positioning fluid source 124i higher than a subject), manually-applied pressure (e.g., pumping, rotating, squeezing, and the like), pressure applied by compressed air, and the like, enables fluid to pass from fluid source 124i through tubes 116i, 120i, and 128i and into the aerodigestive tract of a subject.

[0044] In the embodiment shown, device lOOi comprises catchment 132i, which is positionable (e.g., about a subject's head) to enable fluid exiting the nose and/or the mouth of the subject to be collected in the catchment. Catchment 132i is coupled to pump 104i by exit tube 136i. Fluid in catchment 132i can exit catchment 132i as a result of positive pressure (e.g., hydrostatic pressure), negative pressure (e.g., a vacuum), or both. For example, in the embodiment shown, pump 104i is configured, if activated, to enable fluid to be pumped from catchment 132i through filter 140i and through heat exchanger 144i, which is coupled to chiller 148i such that chiller 148i can cool fluid passing through heat exchanger 144i, and into fluid source 124i. In some embodiments, 132i comprises an active return. In some embodiments, the active return comprises a mask coupled to a tube or a plurality of tubes. In some embodiments, the active return comprises a tube or a plurality of tubes that are inserted into the mouth of the subject. In such an embodiment, where heat exchanger 144i and chiller 148i are disposed downstream from filter 140i, any fluid that is frozen in heat exchanger 144i can flow into fluid source 124i, rather than being filtered, in order to increase cooling of the free-flowing fluid. In the embodiment shown, heat exchange is not electrically isolated (e.g., heat exchanger 144i is in fluid communication with fluid moving through device lOOi). Device lOOi further comprises pressure monitor 152i, which is configured to measure pressure of fluid passing through filter 140i. In the embodiment shown, device lOOi further comprises pinch clamp 156i, which is configured to enable adjustment of fluid flow passing through tubes 116i and 120i, and pinch clamp 160i, which is configured to enable adjustment of fluid flow passing through tube 128i. Fluid flow through tubes 116i and 120i can also be adjusted by adjusting the height of fluid source 124i with respect to a subject and/or by adjusting the diameter of tubes 116i, 120i, and/or 128i. Flow indicator 164i is positioned downstream from pinch claim 156i to measure or provide an indication as to fluid flow such that fluid flow can be optimized using pinch clamp 156i. Similarly, flow indicator 168i is positioned downstream from pinch claim 160i to measure or provide an indication as to fluid flow such that fluid flow can be optimized using pinch clamp 160i. If device lOOi is activated, device lOOi is configured to enable free-flowing cooling fluid (e.g., from fluid source 124i) to pass through tubes 116i, 120i, and/or 128i and into the aerodigestive tract of a subject until a brain to body core temperature gradient of at least 1 °C is reached and/or until a target brain to body core temperature gradient is reached in 30 minutes or less, or both. As explained above, device lOOi (or components thereof, such as one or more pumps) can be coupled to or couplable to a dependent and/or independent power source.

[0045] FIG. 10 depicts another embodiment of the present devices lOOj. Device lOOj of FIG. 10 comprises a similar configuration to device lOOi of FIG. 9, and the components of device lOOj depicted in FIG. 10 can comprise the same or similar functions and characteristics as components depicted and described with respect to device lOOi of FIG. 9. FIG. 10 depicts an embodiment of the present devices in which the devices do not comprise a fluid source independent of internal fluid within the other components of device lOOj. For example, heat exchanger 144j and/or catchment 132j may each or in combination comprise a sufficient volume of fluid such that a separate fluid source is not required to sufficiently cool the aerodigestive tract of a subject. Fluid can be introduced into device lOOj in such an embodiment by, for example, introducing fluid into catchment 132j or a port coupled to heat exchanger 144j. In some embodiments, 132j comprises an active return. In some embodiments, the active return comprises a mask coupled to a tube or a plurality of tubes. In some embodiments, the active return comprises a tube or a plurality of tubes that are inserted into the mouth of the subject. Heat exchanger 144j can be positioned higher than the subject such that hydrostatic pressure can enable fluid to move through device lOOj. Further, pump 104j can additionally enable fluid in such an embodiment to move through device lOOj.

[0046] FIG. 11 depicts another embodiment of the present devices 100k. Device

100k of FIG. 11 comprises a similar configuration to device lOOi of FIG. 9, and the components of device 100k depicted in FIG. 11 can comprise the same or similar functions and characteristics as components depicted and described with respect to device lOOi of FIG. 9. However, device 100k in FIG. 11 does not comprise an independent fluid source apart from fluid in its other internal components, as described with respect to FIG. 10. FIG. 11 depicts an embodiment of the present devices in which flow into tube 116k is not divided by a Y-fitting. Such a tube configuration can be used in any of the other embodiments described and depicted in this disclosure to enable the following. In the embodiment shown, a Y-fitting directs flow from heat exchanger 144k, which can function as a fluid source in FIG. 11, into tubes 116k and 128k. In other embodiments, tube 116k can be coupled to a mask configured to be positioned over at least one of the nose and the mouth of a subject such that free- flowing cooling fluid introduced through tube 116k can enter the aerodigestive tract of the subject. The mask can be suitably sealed with respect to the subject's head to prevent fluid from exiting the mask. For example, in some embodiments, at least a portion of the mask is configured to enlarge if in contact with fluid such that fluid is substantially prevented from exiting the mask (e.g., the mask or a portion thereof can be made with hydrogel). In some embodiments, the mask is further configured to facilitate removing fluid from the aerodigestive tract either passively (e.g., with gravity) or actively (e.g., with a suctioning device or vacuum). In other embodiments, bands coupled to the mask can be tightened/tied about a subject's head. In some embodiments, tube 116k can be configured to be positioned exterior to the nostrils of the subject and to direct fluid into the nasal cavity of the subject. In other embodiments, tube 116k comprises substantially the same shape and/or diameter of a nostril and can be disposed such that tube 116k is adjacent to the nostril of a subject and/or partially interior to the nostril of subject to prevent fluid from exiting the nostril. In some embodiments, tube 116k can be inserted into a nostril a suitable distance to, for example, prevent fluid from exiting the nostril and to prevent tube 116k from exiting the nostril. Tube 116k can be configured to enable introduction of cooling fluid into the nasal cavity of a subject. Tube 116k can also function as, comprise, or be coupled to a stopper such that, if tube 116k and/or tube 128k are positioned exterior to one or more nostrils of the subject, the stopper substantially prevents fluid from exiting the one or more nostrils of the subject. A stopper can comprise substantially the same diameter and/or shape of a nostril of a subject and/or can be made of material configured to conform to the shape of the nose or the nostrils of a subject. Further, a stopper can be disposed outside the nasal vestibule, inside the nasal vestibule, or both outside and inside the nasal vestibule. Similarly, tube 128k can be configured to enable introduction of cooling fluid into the oral cavity of a subject and can also be coupled to a mask (the same or a different mask as tube 116k) as described above. Such configurations can, for example, assist in preventing trauma to the nasal cavity, such as abrasions and associated bleeding (which can be exacerbated by anticoagulants).

[0047] FIG. 12 depicts another embodiment of the present devices 1001. Device 1001 of FIG. 12 comprises a similar configuration to device lOOi of FIG. 9, and the components of device 1001 depicted in FIG. 12 can comprise the same or similar functions and characteristics as components depicted and described with respect to device lOOi of FIG. 9. FIG. 12 depicts an embodiment of the present devices in which pump 1041 comprises a double-headed pump. In the embodiment shown, pump 1041 removes fluid from catchment 1321 through exit tube 1361 (e.g., with a first pump head) such that fluid passes through filter 1401 and heat exchanger 1441 and into fluid source 1241. Pump 1041 also removes fluid from fluid source 1241 (e.g., with a second pump head) through tubes 1161, 1201, and 1281 and into the aerodigestive tract of a subject. In some embodiments, 1321 comprises an active return. In some embodiments, the active return comprises a mask coupled to a tube or a plurality of tubes. In some embodiments, the active return comprises a tube or a plurality of tubes that are inserted into the mouth of the subject.

[0048] FIGS. 1-12 depict various embodiments of the present cooling devices that are each configured to enable free-flowing cooling fluid to pass through a plurality of tubes and into the aerodigestive tract of a subject. FIGS. 1-12 further depict various embodiments of the present cooling devices that are each configured to enable fluid exiting the nose and/or the mouth of the subject to be collected in a catchment for return to the fluid source. The devices in FIGS. 1-12 can be constructed as depicted, or can be modified with components of other embodiments depicted or described, to adapt to an intended use. For example, in some embodiments, a device may be used with a dependent power source and, therefore, weight, size, and energy concerns related to the device may factor less into design considerations; and in other embodiments, a device may be used with an independent power source (e.g., which can enable the device to be mobile/transportable) and, therefore, weight, size, and energy concerns related to the device may factor more into design considerations. In each of the embodiments, one or more components may be added to the embodiment or removed and/or replaced by another component, and the devices may still be enabled to provide free-flowing cooling fluid to pass into the aerodigestive tract of a subject. For example, in some embodiments, the devices may not comprise a catchment such that fluid that has passed through the aerodigestive tract of a subject does not do so again. In some embodiments, the devices may not comprise a fluid source independent of internal fluid within the other components of the devices, such as the embodiments described in FIG. 10 or 11. Further, any component described with respect to FIGS. 1-12 as "coupled" to another component can also be described as "couplable" to that component. Any of the one or more tubes described with respect to FIGS. 1-12, as with any of the embodiments described in this disclosure, can be configured to enable introduction of fluid into the aerodigestive tract of a subject by positioning the one or more tubes exterior to the nose and/or mouth of the subject and directing the one or more tubes interior to the nose and/or mouth of the subject, by coupling the one or more tubes to another device (such as a mask or a nasal pillow), and/or by inserting the one or more tubes interior to the nose and/or mouth of the subject. Moreover, the devices depicted in FIGS. 1-12 comprise one or more heat exchangers, but are not required to. For example, in some embodiments, fluid in a device is cooled using an external device or method, and in some embodiments, fluid in a device is cooled by a chemical reaction, whether external or internal, or an absorptive process.

[0049] Any of the devices described in this disclosure, including those described in

FIGS. 1-12 can further comprise an esophageal blockage configured to be disposed in the oral cavity of a subject such that fluid is at least partially prevented from entering the stomach of the subject. A blockage described in this disclosure can include any object configured to be disposed in the aerodigestive tract of a subject to increase resistance to fluid flow. For example, a blockage can comprise a tube, a stent (e.g., temporary or permanent), an inflatable cuff (e.g., a balloon), a packing material (e.g., gauze, sponges, towels, and the like), and/or a combination thereof. Any blockage of the present disclosure can be configured/sized or configurable/sizable (e.g., by self-expansion, compression, inflation, and the like) to minimize a distance between the blockage and surrounding tissue in the region of the aerodigestive tract in which the blockage is disposed. For example, a blockage can occupy a majority to substantially all of the empty space in a given region of the aerodigestive tract. For example, in some embodiments, a blockage can comprise an inflatable cuff, which can be positioned such that, after the blockage is inserted into the aerodigestive tract of a subject, the blockage can be inflated to increase resistance to cooling fluid flow in a region of the aerodigestive tract (e.g., by applying pressure to nearby structures of the aerodigestive tract to substantially prevent fluid from moving beyond the blockage). In some embodiments, a length of an inflatable cuff is substantially equal to a length of a corresponding blockage; and, in other embodiments, a length of an inflatable cuff is less than or greater than a length of a corresponding blockage. In some embodiments, the esophageal blockage extends at least to the upper esophageal sphincter. In some embodiments, the esophageal blockage extends at least partially into the stomach and blocks the distal side of the upper esophageal sphincter. In other embodiments, the esophageal blockage extends to the lower esophageal sphincter (or immediately prior thereto). In some embodiments, the esophageal blockage is configured to enlarge if in contact with fluid (e.g., the surface of esophageal blockage can comprise hydrogel). In some embodiments, the esophageal blockage is compressible such that, if disposed in the esophagus, the esophageal blockage substantially conforms to the shape of the esophagus. In some embodiments, the esophageal blockage comprises a first end and a second end that are in fluid communication (e.g., to permit access to the stomach of a subject, such as to enable evacuation of the stomach and/or a nasogastric tube to be delivered to the stomach). In some embodiments, the esophageal blockage permits introduction of free- flowing cooling fluid near at least one of the oropharynx and hypopharynx. For example, in some embodiments, esophageal blockage comprises an opening to permit delivery and/or removal of fluid near the oropharynx and hypopharynx, and an esophageal blockage can comprise multiple lumens to permit such delivery and/or removal.

[0050] FIG. 13 depicts one embodiment of board 172 on which a subject can be positioned while cooling the aerodigestive tract of the subject. Board 172 is configured to position the subject's ears, or at least a portion of subject's ears, lower than the subject's back and/or to position the subject's pharynx lower than the subject's trachea (e.g., such that the posterior wall of the pharynx is dependent to the posterior wall of the trachea). Board 172 comprises and/or can be positioned to define or accommodate reservoir 176 in which fluid exiting the subject's nose and/or mouth can collect. In some embodiments, fluid in reservoir 176 can be used as fluid to cool the brain of the subject as described in the devices and methods in this disclosure. For example, board 172 can be used without esophageal obstruction or with partial esophageal obstruction and/or without an endotracheal tube. Board 172 can encourage fluid in the aerodigestive tract of the subject to remain below the larynx and/or carina. Board 172 can be any suitable shape and size configured to accommodate a subject in the manner described and can be adjustable or fixed. For example, board 172 can be approximately shoulder width and extend to the hips or to the feet of a subject, and can be extendible in width or length. As a further example, board 172 can comprise a fixed thickness (e.g., 1-12 inches) or an adjustable thickness. Adjustments could be made to board 172 in any suitable way, such as with air or liquid bladders, mechanically, electrically, and the like. As a further example, board 172 can be configured to be coupled to or sit on top of a backboard, and in other embodiments, board 172 is integral with a backboard (e.g., formed of the same piece of material). [0051] FIG. 14 depicts one embodiment of catchment 180a on which a subject can be positioned while cooling the aerodigestive tract of the subject. Catchment 180a is configured to enable fluid exiting the nose and/or the mouth of the subject to be collected in the catchment. In the embodiment shown, catchment 180a comprises an opening through which fluid in the catchment can exit via exit tube 184a. In some embodiments, fluid exiting catchment 180a can be reused in devices and methods to cool the brain of the subject; and in other embodiments, fluid exiting catchment 180a is not reused. In the embodiment shown, catchment 180a is configured to elevate the subject's neck. In other embodiments, catchment 180a does not elevate the subject's neck and accommodates (e.g., by sealing or partially sealing) the subject's neck so as to prevent fluid from exiting catchment 180a. Catchment 180a can be configured to position a subject's head similarly to board 172 in FIG. 13. Catchment 180a can be any suitable shape and size configured to accommodate a subject (and in the embodiment shown, a subject's head) in the manner described and/or to accommodate fluid exiting the nose and/or mouth of a subject. Catchment 180a can be adjustable or fixed, can comprise a transparent, translucent, or opaque appearance, and/or can comprise a malleable or rigid material. In other embodiments, a subject's head is not placed within catchment 180a, but catchment 180a is positioned such that fluid exiting the mouth and/or nose of the subject collects in catchment 180a. In such an embodiment, it may not be required that a subject is intubated.

[0052] FIG. 15 depicts another embodiment of a catchment 180b on which a subject can be positioned while cooling the aerodigestive tract of the subject. Catchment 180b can comprise a similar configuration to and the same or similar functions and characteristics as catchment device 180b (and the related components) as described with respect to FIG. 14. FIG. 15 further depicts support members 188b and 192b that can be positioned within catchment 180b and/or coupled within catchment 180b such that the subject's head is substantially prevented from contacting fluid that collects in catchment 180b.

[0053] The present disclosure also includes methods of cooling the brain of a subject.

For example, in some embodiments, the methods comprise transporting a device to a subject, where the device is configured to introduce free-flowing cooling fluid through a plurality of tubes into the aerodigestive tract of the subject; introducing free-flowing cooling fluid through the plurality of tubes and into the aerodigestive tract of the subject; and continuing to cool the aerodigestive tract of the subject until a brain to body core temperature gradient of at least 1 °C is reached (e.g., 1 °C, 2 °C, 3 °C, 4 °C, 5 °C, 6 °C, 7 °C, 8 °C, 9 °C, 10 °C, or more). Though not required to be measured during the present methods, brain temperature used to determine the brain to body core temperature can be measured at any suitable location; but in some embodiments, brain temperature used to determine the brain to body core temperature is measured at the jugular bulb of the subject. In other embodiments, the methods comprise transporting a device to a subject, where the device is configured to introduce free-flowing cooling fluid through a plurality of tubes into the aerodigestive tract of the subject; introducing free-flowing cooling fluid through the plurality of tubes and into the aerodigestive tract of the subject; and continuing to cool the aerodigestive tract of the subject until a target brain to body core temperature gradient is reached in 30 minutes or less (e.g., 30 minutes, 25 minutes, 20 minutes, 15 minutes, 10 minutes, 5 minutes, or less). Other embodiments can comprise a combination of a target gradient and a target time to reach the target gradient, such as, for example, cooling the aerodigestive tract of the subject until a target brain to body core temperature gradient of 3 °C is reached in 15 minutes, or such as cooling the aerodigestive tract of the subject until a target brain to body core temperature gradient of 2 °C is reached in 5 minutes, and similar such combinations. A device can be transported to a subject in various ways, such as on foot, by vehicle (e.g., ambulance), or by air (e.g., helicopter). In some embodiments, the methods comprise reducing blood flow to the subject's brain, such as by reducing blood pressure, administering one or more substances, and the like (e.g., with an apparatus configured to reduce blood flow to a subject's brain).

[0054] In some embodiments, the methods further comprise transporting the subject to a destination and continuing to cool the aerodigestive tract of the subject until a brain to body core temperature gradient of at least 1 °C is reached. Such cooling of the aerodigestive tract can continue to be introducing free-flowing cooling fluid through the plurality of tubes of the device into the aerodigestive tract of the subject, or by other intermittent methods described further below. In some embodiments, cooling the aerodigestive tract of a subject includes introducing one or more of the plurality of tubes into the nasal cavity of the subject. In some embodiments, cooling the aerodigestive tract of a subject includes introducing one or more of the plurality of tubes into the oral cavity of the subject. In some embodiments, cooling the aerodigestive tract of a subject includes both introducing one or more of the plurality of tubes into the nasal cavity of the subject and one or more of the plurality of tubes into the oral cavity of the subject. In other embodiments, cooling the aerodigestive tract of a subject includes positioning one or more of the plurality of tubes exterior to one or more nostrils of the subject such that free-flowing cooling fluid moving through the plurality of tubes can enter the aerodigestive tract of the subject through the one or more nostrils. Such a configuration can, for example, assist in preventing trauma to the nasal cavity, such as abrasions and associated bleeding (which can be exacerbated by anticoagulants). Whether one or more tubes are positioned exterior to or interior to the nasal and/or or cavity of a subject, one or more of the tubes can be coupled to a stopper that substantially prevents fluid from exiting the one or more nostrils of the subject. In still other embodiments, cooling the aerodigestive tract of a subject includes coupling one or more of the plurality of tubes to a mask configured to be positioned over at least one of the nose and the mouth of a subject and positioning the mask over at least one of the nose and the mouth of the subject such that free- flowing cooling fluid introduced through the one or more of the plurality of tubes can enter the aerodigestive tract of the subject. In some embodiments, at least a portion of the mask is configured to enlarge if in contact with fluid such that fluid is substantially prevented from exiting the mask. In some embodiments, the mask is further configured to facilitate removing fluid from the aerodigestive tract either passively (e.g., with gravity) or actively (e.g., with a suctioning device or vacuum). Further, combinations of the above-described methods/configurations can be used to cool the aerodigestive tract of a subject.

[0055] The present methods further include intermittent cooling methods, which can, for example, be used prior to, during, or after introduction of free-flowing cooling fluid into the aerodigestive tract of a subject through a plurality of tubes, or a combination thereof. Intermittent cooling methods can be used, for example, if a subject is at risk of aspiration from a continuous flow of fluid, if a device configured to provide a continuous flow of fluid is not available, and/or if rapid introduction of cooling fluid to the aerodigestive tract of a subject to cool the brain is advantageous or required. For example, such methods can include introducing cooling boluses into the oral cavity of the subject, which can comprise 100 to 200 milliliters of cooling fluid. Such methods can also comprise positioning a container (e.g., a squeezable bottle, a bag, and the like) containing free-flowing cooling fluid exterior to or interior to one or more nostrils of the subject and applying pressure to the container such that free-flowing cooling fluid exits the container and is introduced through the one or more nostrils of the subject and into the nasal cavity. Similarly, the methods can also comprise positioning a container containing free-flowing cooling fluid exterior to or interior to the mouth of the subject and applying pressure to the container such that free-flowing cooling fluid exits the container and is introduced through the mouth of the subject and into the oral cavity. Fluid in the container can be cooled prior to entering the container or while in the container by any suitable cooling method, such as with ice, an absorptive process, a chemical reaction (e.g., the container can be made from materials that can create an endothermic reaction, an object can be placed interior to the container that can create an endothermic reaction (e.g., cold pack), and/or fluid entering the container can pass through a component that can create an endothermic reaction), refrigeration, an absorptive process, and the like. In some embodiments, the container is configured to substantially prevent fluid from exiting the one or more nostrils of the subject while free-flowing cooling fluid is being introduced into the nasal cavity of the subject. For example, the container can comprise an end through which fluid exits the container, and such end can comprise a shape and/or size similar to that of a nostril (e.g., a cone-shaped end) such that, if the end is placed exterior to a nostril, fluid is substantially prevented from exiting the nostril. In some embodiments, the methods further comprise introducing a solid-phase coolant into the oral cavity of the subject. Such a coolant can, for example, assist in cooling regions of the aerodigestive track near the pharynx. Solid- phase coolant can then be permitted to melt in the oral cavity. In some embodiments, the solid-phase coolant comprises at least one of saline, ice chips (including ice lentils, ice peas, etc.), ice chips in a base of propylene glycol, ice chips in a base of saline, and/or ice chips in a base of water. In some embodiments, the methods further comprise introducing at least one of an emulsion and a slurry (e.g., partially frozen water in a combined solid and liquid state) into the oral cavity of the subject.

[0056] Some embodiments of the present methods comprise disposing an esophageal blockage in the oral cavity such that fluid is at least partially prevented from entering the stomach of the subject. In some embodiments, the esophageal blockage extends at least to the upper esophageal sphincter. In some embodiments, the esophageal blockage extends at least partially into the stomach and blocks the distal side of the upper esophageal sphincter. In some embodiments, the esophageal blockage is configured to enlarge if in contact with fluid. In some embodiments, the esophageal blockage is compressible such that, if disposed in the esophagus, the esophageal blockage substantially conforms to the shape of the esophagus. In some embodiments, the esophageal blockage comprises a first end and a second end that are in fluid communication. In some embodiments, the esophageal blockage permits introduction of free-flowing cooling fluid near at least one of the oropharynx and hypopharynx.

[0057] Some embodiments of the present methods comprise placing the subject on a board, where the board is configured to position at least a portion of the subject's ears lower than the subject's back. Some embodiments comprise placing the subject on a board, where the board is configured to position the subject's pharynx lower than the subject's trachea. Some embodiments further comprise positioning the subject's head in a catchment to enable fluid exiting the nose and/or the mouth of the subject to be collected in the catchment and removing fluid from the catchment through an opening in the catchment. In some embodiments, the subject's neck is placed in contact with a portion of the catchment to elevate the subject's neck.

[0058] Some embodiments of the present methods comprise positioning the subject's pharynx lower than the subject's trachea. In some embodiments, cooling fluid is introduced and removed from the subject's aerodigestive tract at a rate that prevents the cooling fluid from flowing in to the subject's trachea. In some embodiments, the cooling fluid is delivered and removed through a plurality of tubes. In some embodiments, the volume of cooling fluid in the subject's aerodigestive tract is controlled such that an esophageal blockage or balloon is not required. In some embodiments, the volume of cooling fluid in the subject's aerodigestive tract is controlled such that a balloon preventing fluid flow into the trachea is not required. In some embodiments, no tracheal intubation is required. In some embodiments, the positioning the subject's pharynx lower than the subject's trachea comprises placing the subject on a board where the relative position of the subject's pharynx to the subject's trachea is adjusted by moving the board.

[0059] Some embodiments of the present methods comprise adjusting the subject's carbon dioxide partial pressure (pC0₂) level to decrease cerebral blood flow. In some embodiments, the methods comprise reducing the subject's carbon dioxide partial pressure (pC0₂) level to decrease cerebral blood flow.

Examples

[0060] Some examples of clinical and theoretical implementations of the present devices and methods are described below. These examples are illustrative only and are not meant to provide any limitations to the scope of this disclosure. Recent clinical results indicate that the present methods and devices provide highly selective cooling. Such devices and methods have reached a brain temperature to body core gradient of at least 3.5 and achieved roughly a 3.5 °C in clinical trials. To maintain this gradient, and assuming a cerebral blood flow of 1 liter per minute, blood must be cooled at 3.5 °C per minute. This can be calculated to require approximately 210 Watts: (3.5 °C)*(3.6 J/Kg) *(1000g/60). In some cases, where cerebral blood flow is higher, more power is required, and in some cases where cerebral blood flow is lower, less power is required. For example, if cerebral blood flow was reduced to 500 milliliters per minute or less, which may be the case in some cardiac arrests, a power requirement to produce the same gradient may be approximately 100W or less. [0061] The selectivity and efficiency of the present devices and methods permits even relatively small devices to have a meaningful impact. A cold source consisting of 2 Kg of ice could provide 30 minutes of cooling at power that is more than sufficient to have a beneficial effect. In the event that a cold source must be supplied apart from an independent power source, such as an electrical grid, cold may be rapidly generated in situ by endothermic reaction (such as by ammonium nitrate and water and ammonium chloride and water).

[0062] Additional thermochemical cooling schemes can use "adsorption refrigeration." In this scheme an adsorbent having a high surface area, such as zeolite, silica gel, and/or activated carbon is dried and sealed under vacuum into a module. When needed, the module can be connected to a supply of fluid to be cooled, such as water or methanol, and the adsorbent begins to attract vapor from the fluid, cooling the fluid. Such an embodiment does not require refrigeration and uses ingredients that are highly inert and environmentally benign. As an example, a zeolite-water refrigerator of 2 Kg zeolite adsorbs 300 g water and can remove 690 KJ of energy from the target water reservoir. Such an embodiment can provide sufficient power for an emergency application where electricity may not be available.

[0063] The overall rate of this heat transfer process can be represented by the following equation:

1

q = : — ; A Tblood— Twater)

1 _| tissue thickness _| 1 ^J h water) k(tissue) h(blood)

[0064] Values have been introduced in the following equation:

1

q =— οΊ₎Ϊ5 —A(Tblood— Twater)

300 ^{+ ~}O5^{~ +} 220

[0065] As another example, if blood flow is assumed to be 500 ml/min and water is delivered to both the nose and the esophagus at 1.5 L/min, for a total of 3 L/min, there is approximately a 1 °C increase in water temperature for every 6 °C drop in arterial blood temperature at steady state.

[0066] Assuming the total volume of the esophagus and pharynx is less than 300 ml, sweeping the esophagus and pharynx with 3 IV min of water will remain in the aerodigestive tract for approximately 6 seconds. If water remained in the aerodigestive tract for approximately 60 seconds, which corresponds to a flow rate of about 300 ml/min, then the water temperature may be predicted to increase by about 10 °C, which would decrease the driving force for heat transfer by about 30%.

[0067] This amount of flow can be provided by manual pumping of 300 ml of cold water into the patient's aerodigestive tract and leaving it in place to cool a subject for 1 minute, after which time it could be replaced by a bolus of 300 ml of cold water. Water or saline could be recaptured in a catchment, re-cooled and returned, or discarded.

[0068] The above specification and examples provide a complete description of the structure and use of exemplary embodiments. Although certain embodiments have been described above with a certain degree of particularity, or with reference to one or more individual embodiments, those skilled in the art could make numerous alterations to the disclosed embodiments without departing from the scope of this invention. As such, the various illustrative embodiments of the present devices and methods are not intended to be limited to the particular forms disclosed. Rather, they include all modifications and alternatives falling within the scope of the claims, and embodiments other than the one shown may include some or all of the features of the depicted embodiment. For example, components may be combined as a unitary structure and/or connections may be substituted. Further, where appropriate, aspects of any of the examples described above may be combined with aspects of any of the other examples described to form further examples having comparable or different properties and addressing the same or different problems. Similarly, it will be understood that the benefits and advantages described above may relate to one embodiment or may relate to several embodiments.

[0069] The claims are not intended to include, and should not be interpreted to include, means-plus- or step-plus-function limitations, unless such a limitation is explicitly recited in a given claim using the phrase(s) "means for" or "step for," respectively.

Claims

1. A method for cooling the brain, comprising:

transporting a device to a subject, where the device is configured to introduce free- flowing cooling fluid through a plurality of tubes into the aerodigestive tract of the subject;

introducing free-flowing cooling fluid through the plurality of tubes and into the

aerodigestive tract of the subject; and

continuing to cool the aerodigestive tract of the subject until a brain to body core temperature gradient of at least 1 °C is reached.

2. The method of claim 1, further comprising:

transporting the subject to a destination; and

3. The method of claim 1, further comprising:

transporting the subject and the device to a destination; and

continuing to introduce free-flowing cooling fluid through the plurality of tubes of the device into the aerodigestive tract of the subject until brain to body core temperature gradient of at least 1 °C is reached.

4. The method of claim 1, further comprising:

reducing blood flow to the subject's brain.

5. The method of claim 1, where the temperature gradient of at least 1 °C is reached in 30 minutes or less.

6. The method of claim 1, where the temperature gradient of at least 1 °C is reached in 25 minutes or less.

7. The method of claim 1, where the temperature gradient of at least 1 °C is reached in 20 minutes or less.

8. The method of claim 1, where the temperature gradient of at least 1 °C is reached in 15 minutes or less.

9. The method of claim 1, where the temperature gradient of at least 1 °C is reached in 10 minutes or less.

10. The method of claim 1, where the temperature gradient of at least 1 °C is reached in 5 minutes or less.

11. The method of claim 1 , where a brain to body core temperature gradient of at least 2 °C is reached.

12. The method of claim 1, where a brain to body core temperature gradient of at least 3 °C is reached.

13. The method of claim 1, where a brain to body core temperature gradient of at least 4 °C is reached.

14. The method of claim 1, where a brain to body core temperature gradient of at least 5 °C is reached.

15. The method of claim 1, where a brain to body core temperature gradient of at least 6 °C is reached.

16. The method of claim 1, where a brain to body core temperature gradient of greater than 6 °C is reached.

17. The method of claim 1 , where a brain temperature is measured at the jugular bulb of the subject and is used to determine the brain to body core temperature gradient.

18. The method of claim 1, further comprising:

introducing one or more of the plurality of tubes into the nasal cavity of the subject.

19. The method of claim 1, further comprising:

introducing one or more of the plurality of tubes into the oral cavity of the subject.

20. The method of claim 1, further comprising:

introducing one or more of the plurality of tubes into the nasal cavity of the subject and one or more of the plurality of tubes into the oral cavity of the subject.

21. The method of claim 1 , further comprising:

positioning one or more of the plurality of tubes exterior to one or more nostrils of the subject such that free-flowing cooling fluid moving through the plurality of tubes can enter the aerodigestive tract of the subject through the one or more nostrils.

22. The method of claim 21, where one or more of the plurality of tubes is each coupled to a stopper that, if the one or more tubes are positioned exterior to one or more nostrils of the subject, substantially prevents fluid from exiting the one or more nostrils of the subject.

23. The method of claim 1, further comprising:

coupling one or more of the plurality of tubes to a mask configured to be positioned over at least one of the nose and the mouth of a subject; and

positioning the mask over at least one of the nose and the mouth of the subject such that free-flowing cooling fluid introduced through the one or more of the plurality of tubes can enter the aerodigestive tract of the subject.

24. The method of claim 23, where at least a portion of the mask is configured to enlarge if in contact with fluid such that fluid is substantially prevented from exiting the mask.

25. The method of claim 23, where the mask is further configured to facilitate removing fluid from the aerodigestive tract.

26. The method of claim 25, where the fluid is actively removed.

27. The method of claim 1, where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the method further comprising:

introducing cooling boluses into the oral cavity of the subject.

28. The method of claim 27, where the boluses comprise 100 to 200 milliliters of cooling fluid.

29. The method of claim 1, where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the method further comprising:

positioning a container containing free-flowing cooling fluid exterior to or interior to one or more nostrils of the subject; and

applying pressure to the container such that free-flowing cooling fluid exits the

container and is introduced through the one or more nostrils of the subject and into the nasal cavity.

30. The method of claim 29, where the container is configured to substantially prevent fluid from exiting the one or more nostrils of the subject while free-flowing cooling fluid is being introduced into the nasal cavity of the subject.

31. The method of claim 1 , where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the method further comprising: introducing a solid-phase coolant into the oral cavity of the subject.

32. The method of claim 31 , where the solid-phase coolant comprises at least one of saline, ice chips, and ice chips in a base of propylene glycol.

33. The method of claim 1, where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the method further comprising:

introducing at least one of an emulsion and a slurry into the oral cavity of the subject.

34. The method of claim 1, where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the method further comprising:

positioning a container containing free-flowing cooling fluid exterior to or interior to the mouth of the subject; and

container and is introduced into the oral cavity of the subject.

35. The method as in any of claims 1-34, further comprising:

disposing an esophageal blockage in the oral cavity such that fluid is at least partially prevented from entering the stomach of the subject.

36. The method of claim 35, where the esophageal blockage extends at least to the upper esophageal sphincter.

37. The method of claim 36, where the esophageal blockage extends at least partially into the stomach and blocks the distal side of the upper esophageal sphincter.

38. The method of claim 35, where the esophageal blockage is configured to enlarge if in contact with fluid.

39. The method of claim 35, where the esophageal blockage is compressible such that, if disposed in the esophagus, the esophageal blockage substantially conforms to the shape of the esophagus.

40. The method of claim 35, where the esophageal blockage comprises a first end and a second end that are in fluid communication.

41. The method of claim 35, where the esophageal blockage permits introduction of free- flowing cooling fluid near at least one of the oropharynx and hypopharynx.

42. The method as in any of claims 1-41, further comprising: placing the subject on a board, where the board is configured to position at least a portion of the subject's ears lower than the subject's back.

43. The method as in any of claims 1-42, further comprising:

placing the subject on a board, where the board is configured to position the subject's pharynx lower than the subject's trachea.

44. The method as in any of claims 1-43, further comprising:

positioning the subject's head in a catchment to enable fluid exiting at least one of the nose and the mouth of the subject to be collected in the catchment;

removing fluid from the catchment through an opening in the catchment.

45. The method of claim 44, where the subject's neck is placed in contact with a portion of the catchment to elevate the subject's neck.

46. The method of claim 1, further comprising:

adjusting the subject's carbon dioxide partial pressure (pC0₂) level to decrease

cerebral blood flow.

47. The method of claim 1, further comprising:

reducing the subject's carbon dioxide partial pressure (pC0₂) level to decrease

cerebral blood flow.

48. The method as in any of claims 1-48, where the free-flowing cooling fluid is cooled by an external device.

49. The method as in any of claims 1-49, where the free-flowing cooling fluid is cooled by a chemical reaction or an absorptive process.

50. A method for cooling the brain, comprising:

aerodigestive tract of the subject; and

continuing to cool the aerodigestive tract of the subject until a target brain to body core temperature gradient is reached in 30 minutes or less.

51. The method of claim 50, further comprising:

transporting the subject to a destination; and continuing to cool the aerodigestive tract of the subject until a target brain to body core temperature gradient is reached in 30 minutes or less.

52. The method of claim 50, further comprising:

transporting the subject and the device to a destination; and

continuing to introduce free-flowing cooling fluid through the plurality of tubes of the device into the aerodigestive tract of the subject until a target brain to body core temperature gradient is reached in 30 minutes or less.

53. The method of claim 50, further comprising:

reducing blood flow to the subject's brain.

54. The method of claim 50, where the target brain to body core temperature gradient is reached in 25 minutes or less.

55. The method of claim 50, where the target brain to body core temperature gradient is reached in 20 minutes or less.

56. The method of claim 50, where the target brain to body core temperature gradient is reached in 15 minutes or less.

57. The method of claim 50, where the target brain to body core temperature gradient is reached is reached in 10 minutes or less.

58. The method of claim 50, where the target brain to body core temperature gradient is reached in 5 minutes or less.

59. The method of claim 50, where the target brain to body core temperature gradient is at least 1 °C.

60. The method of claim 50, where the target brain to body core temperature gradient is at least 2 °C.

61. The method of claim 50, where the target brain to body core temperature gradient is at least 3 °C.

62. The method of claim 50, where the target brain to body core temperature gradient is at least 4 °C.

63. The method of claim 50, where the target brain to body core temperature gradient is at least 5 °C.

64. The method of claim 50, where the target brain to body core temperature gradient is at least 6 °C.

65. The method of claim 50, where the target brain to body core temperature gradient is greater than 6 °C.

66. The method of claim 50, where a brain temperature is measured at the jugular bulb of the subject and is used to determine the brain to body core temperature gradient.

67. The method of claim 50, further comprising:

68. The method of claim 50, further comprising:

69. The method of claim 50, further comprising:

70. The method of claim 50, further comprising:

71. The method of claim 70, where one or more of the plurality of tubes is each coupled to a stopper that, if the one or more tubes are positioned exterior to one or more nostrils of the subject, substantially prevents fluid from exiting the one or more nostrils of the subject.

72. The method of claim 50, further comprising:

73. The method of claim 72, where at least a portion of the mask is configured to enlarge if in contact with fluid such that fluid is substantially prevented from exiting the mask.

74. The method of claim 72, where the mask is further configured to facilitate removing fluid from the aerodigestive tract.

75. The method of claim 74, where the fluid is actively removed.

76. The method of claim 50, where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the method further comprising:

introducing cooling boluses into the oral cavity of the subject.

77. The method of claim 76, where the boluses comprise 100 to 200 milliliters of cooling fluid.

78. The method of claim 50, where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the method further comprising:

79. The method of claim 78, where the container is configured to substantially prevent fluid from exiting the one or more nostrils of the subject while free-flowing cooling fluid is being introduced into the nasal cavity of the subject.

80. The method of claim 50, where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the method further comprising:

introducing a solid-phase coolant into the oral cavity of the subject.

81. The method of claim 80, where the solid-phase coolant comprises at least one of saline, ice chips, and ice chips in a base of propylene glycol.

82. The method of claim 50, where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the method further comprising:

83. The method of claim 50, where prior to or after introducing free-flowing cooling fluid through the plurality of tubes, the method further comprising:

container and is introduced into the oral cavity of the subject.

84. The method as in any of claims 50-83, further comprising:

85. The method of claim 84, where the esophageal blockage extends at least to the upper esophageal sphincter.

86. The method of claim 85, where the esophageal blockage extends at least partially into the stomach and blocks the distal side of the upper esophageal sphincter.

87. The method of claim 84, where the esophageal blockage is configured to enlarge if in contact with fluid.

88. The method of claim 84, where the esophageal blockage is compressible such that, if disposed in the esophagus, the esophageal blockage substantially conforms to the shape of the esophagus.

89. The method of claim 84, where the esophageal blockage comprises a first end and a second end that are in fluid communication.

90. The method of claim 84, where the esophageal blockage permits introduction of free- flowing cooling fluid near at least one of the oropharynx and hypopharynx.

91. The method as in any of claims 50-90, further comprising:

placing the subject on a board, where the board is configured to position at least a portion of the subject's ears lower than the subject's back.

92. The method as in any of claims 50-91, further comprising:

93. The method as in any of claims 50-92, further comprising:

removing fluid from the catchment through an opening in the catchment.

94. The method of claim 93, where the subject's neck is placed in contact with a portion of the catchment to elevate the subject's neck.

95. The method of claim 50, further comprising: adjusting the subject's carbon dioxide partial pressure (pC0₂) level to decrease cerebral blood flow.

96. The method of claim 50, further comprising:

cerebral blood flow.

97. The method as in any of claims 50-97, where the free-flowing cooling fluid is cooled by an external device.

98. The method as in any of claims 50-98, where the free-flowing cooling fluid is cooled by a chemical reaction or an absorptive process.

99. A device for cooling the brain, the device comprising:

an power source;

a pump coupled to the power source;

a plurality of tubes coupled to a fluid source;

where the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a brain to body core temperature gradient of at least 1 °C is reached.

100. A device for cooling the brain, the device comprising:

a power source;

a pump coupled to the power source;

a plurality of tubes coupled to a fluid source;

where the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a target brain to body core temperature gradient is reached in 30 minutes or less.

101. The device as in claim 99 or 100, further comprising:

a catchment positionable to enable fluid exiting at least one of the nose and the mouth of the subject to be collected in the catchment, the catchment coupled to the pump with an exit tube;

where the pump is configured, if activated, to enable fluid to be pumped from the catchment.

102. The device of claim 101, further comprising pinch clamps coupled to one or more of the plurality of tubes to enable flow through the one or more of the plurality of tubes to be adjusted.

103. The device as in any of claims 99-102, where at least one of a positive pressure or a hydrostatic pressure enables free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of the subject.

104. The device as in any of claims 99-103, further comprising:

a heat exchanger.

105. The device as in any of claims 99-104, further comprising:

where the heat exchanger is the fluid source.

106. The device as in claim 99 or 100, where the pump is a first pump, the device further comprising:

a second pump; and

a catchment positionable to enable fluid exiting at least one of the nose and the mouth of the subject to be collected in the catchment, the catchment coupled to an exit tube;

where the first pump and the second pump are each configured, if activated, to enable free-flowing cooling fluid to be pumped through one or more of the plurality of tubes and into the aerodigestive tract of a subject.

107. The device as in any of claims 99-106, further comprising:

a third pump, where the third pump is configured, if activated, to enable free-flowing cooling fluid to be removed from the catchment.

108. The device of claim 107, where the third pump is a vacuum.

109. The device as in any of claims 106-107, where a flow rate of each of the first pump, the second pump, and the third pump can be adjusted independently.

110. The device as in any of claims 101-102 or 106-109, further comprising:

one or more filters; and

one or more heat exchangers coupled to the one or more filters;

where fluid exiting the catchment passes through the one or more filters and

subsequently passes through the one or more heat exchangers.

111. The device as in any of claims 101-102 or 106-109, further comprising: one or more filters; and

one or more heat exchangers coupled to the one or more filters;

where fluid exiting the catchment passes through the one or more heat exchangers and subsequently passes through the one or more filters.

112. The device as in any of claims 99-112, where the fluid source is under a vacuum.

113. The device as in any of claims 99-113, where one or more of the heat exchangers is electrically isolated.

114. The device as in any of claims 99-113, further comprising:

one or more pressure monitors configured to measure pressure of free-flowing cooling fluid in one or more of the plurality of tubes.

115. The device as in any of claims 110-114, where the one or more heat exchangers are the fluid source.

116. The device as in any of claims 99-115, where one or more pumps is a double-headed pump, a roller pump, or a centrifugal pump.

117. The device as in any of claims 99-116, where the power source comprises manual power.

118. The device as in any of claims 99-116, where the power source comprises chemical power.

119. The device as in any of claims 99-118, where the device comprises an outlet plug that enables the device to be coupled to a secondary power source.

120. The device as in any one of claims 99 or 100, where the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a brain to body core temperature gradient of at least 2 °C is reached.

121. The device as in any one of claims 99 or 100, where the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a brain to body core temperature gradient of at least 3 °C is reached.

122. The device as in any one of claims 99 or 100, where the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a brain to body core temperature gradient of at least 4 °C is reached.

123. The device as in any one of claims 99 or 100, where the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a brain to body core temperature gradient of at least 5 °C is reached.

124. The device as in any one of claims 99 or 100, where the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a brain to body core temperature gradient of at least 6 °C is reached.

125. The device as in any one of claims 99 or 100, where the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a brain to body core temperature gradient of greater than 6 °C is reached.

126. The device as in any one of claims 99 or 100, where the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a target brain to body core temperature gradient is reached in 25 minutes or less.

127. The device as in any one of claims 99 or 100, where the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a target brain to body core temperature gradient is reached in 20 minutes or less.

128. The device as in any one of claims 99 or 100, where the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a target brain to body core temperature gradient is reached in 15 minutes or less.

129. The device as in any one of claims 99 or 100, where the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a target brain to body core temperature gradient is reached in 10 minutes or less.

130. The device as in any one of claims 99 or 100, where the device is configured, if activated, to enable free-flowing cooling fluid to pass through the plurality of tubes and into the aerodigestive tract of a subject until a target brain to body core temperature gradient is reached in 5 minutes or less.

131. The device as in any one of claims 99 or 100, where the device is configured to enable blood flow to the subject's brain to be reduced.

132. The device as in any one of claims 99 or 100, where a brain temperature is measured at the jugular bulb of the subject and is used to determine the brain to body core temperature gradient.

133. The device as in any one of claims 99 or 100, where one or more of the plurality of tubes are configured to be introduced into the nasal cavity of the subject.

134. The device as in any one of claims 99 or 100, where one or more of the plurality of tubes are configured to be introduced into the oral cavity of the subject.

135. The device as in any one of claims 99 or 100, where one or more of the plurality of tubes are configured to be introduced into the nasal cavity of the subject, and one or more of the plurality of tubes is configured to be introduced into the oral cavity of the subject.

136. The device as in any one of claims 99 or 100, where one or more of the of the plurality of tubes are configured to be positioned exterior to one or more nostrils of the subject such that free-flowing cooling fluid moving through the plurality of tubes can enter the aerodigestive tract of the subject through the one or more nostrils.

137. The device of claim 136, further comprising:

a stopper coupled to at least one of the one or more tubes such that, if the one or more tubes are positioned exterior to one or more nostrils of the subject, the stopper substantially prevents fluid from exiting the one or more nostrils of the subject.

138. The device as in any one of claims 99 or 100, further comprising:

a mask coupled to one or more of the plurality of tubes, the mask configured to be positioned over at least one of the nose and the mouth of a subject such that free-flowing cooling fluid introduced through the one or more of the plurality of tubes can enter the aerodigestive tract of the subject.

139. The device of 116.64, where at least a portion of the mask is configured to enlarge if in contact with fluid such that fluid is substantially prevented from exiting the mask.

140. The method of claim 138, where the mask is further configured to facilitate removing fluid from the aerodigestive tract.

141. The method of claim 140, where the fluid is actively removed.

142. The device as in any of claims 99-100 or 119-139, further comprising:

an esophageal blockage configured to be disposed in the oral cavity such that fluid is at least partially prevented from entering the stomach of the subject.

143. The device of claim 142, where the esophageal blockage extends at least to the upper esophageal sphincter.

144. The device of claim 142, where the esophageal blockage extends at least partially into the stomach and blocks the distal side of the upper esophageal sphincter.

145. The device of claim 142, where the esophageal blockage is configured to enlarge if in contact with fluid.

146. The device of claim 142, where the esophageal blockage is compressible such that, if disposed in the esophagus, the esophageal blockage substantially conforms to the shape of the esophagus.

147. The device of claim 142, where the esophageal blockage comprises a first end and a second end that are in fluid communication.

148. The device of claim 142, where the esophageal blockage permits introduction of free- flowing cooling fluid near at least one of the oropharynx and hypopharynx.

149. The device as in any of claims 99-100 or 119-148, further comprising:

a board configured to position at least a portion of the subject's ears lower than the subject's back.

150. The device as in any of claims 99-100 or 119-148, further comprising:

a board configured to position the subject's pharynx lower than the subject's trachea.

151. The device as in any of claims 99-100 or 119-148, further comprising:

a catchment configured to enable fluid exiting at least one of the nose and the mouth of the subject to be collected in the catchment, the catchment comprising an opening through which fluid in the catchment can exit.

152. The device of claim 151, where the catchment is configured to elevate the subject's neck.

153. The device as in any of claims 119-153, where the free-flowing cooling fluid is cooled by an external device.

154. The device as in any of claims 119-154, where the free-flowing cooling fluid is cooled by a chemical reaction or an absorptive process.

155. The device of claim 101, where the pump is configured, if activated, to enable free- flowing cooling fluid to be pumped through one or more of the plurality of tubes and into the aerodigestive tract of a subject and to enable fluid to be pumped from the catchment.

156. The device as in any of claims 99-155, where the power source is an independent power source.