Devices for controlling patient temperature

ES 2 575 302 T3

DESCRIPTION

Devices to monitor the patient's temperature

Background of the invention

In industrial countries, 36 to 128 people per 100,000 inhabitants suffer sudden out-of-hospital cardiac arrest (OHCA) each year, where survival is a rare event. Cardiovascular disease affects an estimated 80,700,000 American adults, with approximately 2,400 individuals dying daily from cardiovascular disease (on average, one death every 37 seconds). Approximately 310,000 deaths from coronary heart disease occur annually due to OHCA.

According to data reported by the National Cardiopulmonary Resuscitation Registry in 2007, more than 75% of patients with cardiopulmonary arrest did not survive the event. Of those who did survive the event, an additional 35.2% died afterward.

In the 1950s, moderate hypothermia (body temperature approximately 28 ° C to approximately 32 ° C) and severe hypothermia (body temperature approximately <28 ° C) were used for various surgical procedures as well as to experimentally reverse neurological lesions associated with Cardiac arrests. However, due to the numerous complications of moderate to severe hypothermia and the difficulty in inducing these temperature reductions, enthusiasm for the use of therapeutic hypothermia waned. Consequently, the use of hypothermia to help reverse neurological damage after normothermic cardiac arrest remained inactive for several decades. However, beginning in the late 1980s, positive results were reported after cardiac arrest in mildly hypothermic dogs.

The contemporary use of mild therapeutic hypothermia after cardiac arrest in human patients is based on recent randomized control trials and a meta-analysis of individual patient data. Leading organizations, including the International Unification Committee on Resuscitation (ILCOR) and the American Heart Association (AHA), have recommended induction of mild therapeutic hypothermia for survivors of comatose cardiac arrest. However, there is no concrete description of exactly how to cool patients in the AHA guidelines for therapeutic hypothermia.

Despite extensive support for mild therapeutic hypothermia in the setting of cardiac arrest, including consensus recommendations from leading resuscitation organizations, the use of mild therapeutic hypothermia in clinical practice remains low. Many clinicians report that therapeutic hypothermia is technically very difficult to achieve in practice.

Additionally, healthcare professionals occasionally need to induce hypothermia during certain surgical procedures or prevent inadvertent hypothermia and the many adverse effects that result from uncontrolled and unintended deviations from normal body temperature.

Monitoring a patient's body temperature while undergoing surgical procedures in the operating room is beneficial as, for example, even mild inadvertent hypothermia during surgical procedures increases the incidence of wound infection, prolongs hospitalization, increases incidence of pathological cardiac events and ventricular tachycardia, and impairs coagulation.

Even mild hypothermia (<1 ° C) significantly increases blood loss by approximately 16% and increases the relative risk for transfusion by approximately 22%, while maintaining perioperative normothermia reduces blood loss and blood requirements for transfusion in clinically important amounts.

Because strong and considerable evidence shows that thermal management improves outcomes in a variety of surgical patients, the 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgeries current from the American Heart Association-American College of Cardiology include a Level 1 recommendation to maintain perioperative normothermia.

In addition to recognizing the many complications of perioperative hypothermia, the American Society of Anesthesiology (ASA) has recently recommended that postoperative temperature become a basis for evaluating medical compliance with current guidelines on the prevention of hypothermia.

Although inadvertent operative hypothermia is considered one of the most preventable surgical complications, existing methods of controlling body temperature are limited in efficacy, such that the incidence of inadvertent operative hypothermia in surgical patients can exceed 50%.

Current methods available to control body temperature include invasive and non-invasive techniques.

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For example, the most commonly used techniques developed to induce therapeutic hypothermia include superficial cooling and invasive cooling.

Surface cooling is relatively simple to use, and can be accomplished through the use of outer jackets, cooling helmets, cold water circulation blankets, forced air cold blankets, or with less sophisticated methods such as ice packs and immersion in cold water, but it takes 2 to 8 hours to lower core body temperature. Superficial cooling is limited by the rate at which cooling can occur, due to the tendency of blood flow to bypass the skin and into the nucleus. External devices, such as vests or blankets, significantly limit access to important patient areas that often require intensive care, such as catheter placement, and require removal or modification to perform CPR. Surface cooling techniques such as ice packs limit the precision with which a patient's temperature can be controlled. Cooling with ice packs and conventional cooling blankets often results in unintentional supercooling.

As another example, various methods are used to warm a patient, and include raising the temperature of the operating room and using external warming devices, such as forced air heating blankets.

There are several problems with these current methods: (1) the excessively hot room temperature creates an uncomfortable environment for the surgical team, (2) forced air heaters are bulky and can impact the surgical field; These tend to be inefficient and must be used for extended periods of time in the OR, and (3) none of these systems controls or manages temperature adequately, leading to overheating or, more often, improper heating.

Rasmussen et al. Paper (Forced-air surface warming versus oesophageal heat exchanger in the prevention of perioperative hypothermia. Acta Anaesthesiol Scand. 1998 Mar; 42 (3): 348-52) mentions that forced air heating of the upper body is effective in maintaining normothermia in patients undergoing abdominal surgeries of an estimated duration of at least 2 h, while central heating with an esophageal heat exchanger is not enough to prevent hypothermia. The document by Brauer et al. (Oesophageal heat exchanger in the prevention of perioperative hypothermia. Acta Anaesthesiol Scand. 1998 Mar; 42 (10): 1232-33) states that an esophageal heat exchanger can only add a small amount of heat to the total body heat balance.

Invasive temperature management treatments include: infusion of cold intravenous fluids; infusion of warm intravenous fluids; cold infusions on the carotid; single carotid artery perfusion with cooled extracorporeal blood; cardiopulmonary bypass; nasal wash with ice water; cold peritoneal lavage; nasogastric and rectal lavage; and the placement of invasive intravenous catheters connected to heat exchange or refrigerant (warming) devices. Invasive temperature management treatments often require the involvement and attention of enough staff to be carried out successfully. In addition, certain invasive modalities of temperature management have been associated with overcooling, overheating, or, more often, improper heating.

The use of intravenous fluid as a temperature management modality has the undesired effect of contributing to circulating fluid volume saturation, and has been found to be insufficient to maintain the target temperature. Additionally, large volumes of fluids must be infused to obtain a significant effect.

Other techniques to achieve hypothermia include cooling the blood using inhaled gases and the use of balloon catheters.

However, the Andrews et al. Paper (Randomized controlled trial of effects of the airflow through the upper respiratory tract of intubated brain-injured patients on brain temperature and selective brain cooling. Br. J. Anaesthesia. 2005; 94 (3): 330-335) mentions that a flow of humidified air at room temperature through the upper airways of intubated patients with brain lesions did not produce clinically relevant or statistically significant reductions in brain temperature.

The paper by Dohi et al. (Positive selective brain cooling method: a novel, simple, and selective nasopharyngeal brain cooling method. Acta Neurochirgurgica. 2006; 96: 409-412) mentions that a Foley balloon catheter inserted to direct The cooled air in the nasal cavity, when used in combination with the cooling of the head by electric fans, selectively lowers the temperature of the brain.

Holt et al. Paper (General hypothermia with intragastric cooling. Surg. Gynecol Obstet. 1958; 107 (2): 251-54; General hypothermia with intragastric cooling: a further study. Surg Forum. 1958; 9: 287-91) mentions the use of an intragastric balloon in combination with heating blankets to produce hypothermia in patients undergoing surgical procedures.

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Similarly, the Barnard paper (Hypothermia: a method of intragastric cooling. Br. J. Surg. 1956; 44 (185): 29698) mentions the use of an intragastric balloon to induce hypothermia by intragastric cooling.

Lasheras United States Patent Application Publication 2004/0199229 mentions heating or cooling by a balloon inserted into the colon of a patient.

US Patent Application Publication 2004/0210281 to Dzeng et al. Mentions a transesophageal balloon catheter for specifically cooling the heart and dismisses technologies that cool the entire body.

Mayse et al. United States Patent Application Publication 2007/0055328 mentions a balloon catheter for protecting the digestive tract of a person undergoing cardiac ablation to correct cardiac arrhythmia.

US Patent 6,607,517 to Dae et al. Is generally directed to the use of endovascular cooling to treat congestive heart failure.

Various complications are known to result from increased pressure within the gastrointestinal tract, as can occur with an inflated balloon within the stomach, colon, or other gastrointestinal organ. For example, inflated stomach can cause intestinal regurgitation, aspiration, and rupture that can result in pneumonia, esophageal tears, colon necrosis, and intestinal ischemia.

Additionally, various modalities of temperature control, particularly those using inflatable balloons, limit the healthcare provider's access to particular anatomical structures that may be crucial to patient care, such as the stomach. These modalities may require that they be withdrawn or modified to achieve adequate treatment.

To date, no modality has been found available to control the patient's temperature that adequately overcomes the technical, logistical, and financial barriers that exist. The ideal patient temperature monitoring device has yet to be developed.

US Patent Publication No. 2008/161890 A1 describes an esophageal heat transfer device with lumens that provide a fluid path for the flow of a heat transfer medium.

In summary, the state of the art related to patient temperature control encompasses at least one significant long-standing need: methods and devices for efficient, safe, and rapid control of patient temperature while maintaining access. to anatomical areas necessary for further treatment. The present technology identifies various indications, diseases, disorders, and conditions that can be treated or prevented by controlling the patient's temperature, and further provides relatively non-invasive methods and devices to quickly and efficiently control the patient's temperature while reducing temperatures. risks generated by the above devices and methods. Furthermore, certain modalities of the present technology provide relatively non-invasive methods and devices for quickly and efficiently controlling the patient's temperature, while at the same time maintaining access to important anatomical structures.

Brief summary of the invention

At least one aspect of the present technology provides one or more methods for inducing systemic hypothermia. The methods comprise inserting a heat transfer device, including a fluid path defined by a fluid inlet lumen and a fluid outlet lumen, into the esophagus of a patient; initiating the flow of a cooling medium along the fluid path; and circulating the medium along the fluid path for a time sufficient to induce systemic hypothermia in the patient. The heat transfer device can include a discrete heat transfer region that is limited to the esophagus of the patient. The patient can be kept in a hypothermic state for at least about two hours, for example. The methods may further comprise monitoring at least one physiological parameter of the patient, such as body temperature. The methods may further comprise maintaining the patient's body temperature below about 34 ° C.

At least one aspect of the present technology provides one or more methods for monitoring core body temperature in a subject. The methods comprise inserting a heat transfer device, including a fluid path defined by a fluid inlet lumen and a fluid outlet lumen, into the esophagus of a subject; initiating the flow of a heat transfer medium along the fluid path; and circulating the medium along the fluid path for a time sufficient to control core body temperature in a subject. The heat transfer device can include a discrete heat transfer region that is limited to the esophagus of the patient. The subject's core body temperature can be monitored for at least about two hours, for example. The methods may further comprise monitoring at least one parameter

ES 2 575 302 T3 physiological of the subject, such as body temperature. The methods may further comprise maintaining the patient's body temperature, for example, below about 34 ° C, between about 34 ° C and about 37 ° C, or about 37 ° C.

At least one aspect of the present technology provides one or more esophageal heat transfer devices. The devices comprise: a plurality of lumens configured to provide a fluid path for the flow of a heat transfer medium; a proximal end including an inlet port and an outlet port; a distal end configured for insertion into a patient's esophagus. The devices may further comprise a hollow tube having a distal end configured to extend into the stomach of the patient. The devices may further comprise an antibacterial coating.

At least one aspect of the present technology provides one or more methods for treating or preventing ischemia-reperfusion injury or injury caused by an ischemic condition. The methods comprise inserting a heat transfer device, including a fluid path defined by a fluid inlet lumen and a fluid outlet lumen, into the esophagus of a patient; initiating the flow of a cooling medium along the fluid path; and circulating the cooling medium along the fluid path for a time sufficient to induce systemic hypothermia in the patient.

At least one aspect of the present technology provides one or more methods for treating or preventing cardiac or neurological injury. The methods comprise inserting a heat transfer device, including a fluid path defined by a fluid inlet lumen and a fluid outlet lumen, into the esophagus of a patient; initiating the flow of a cooling medium along the fluid path; and circulating the cooling medium along the fluid path for a time sufficient to induce systemic hypothermia in the patient. Neurological injury can be associated with, for example, seizures (including ischemic attacks), traumatic brain injury, spinal cord injury, subarachnoid hemorrhage, out-of-hospital cardiopulmonary arrest, hepatic encephalopathy, perinatal asphyxia, hypoxic-anoxic encephalopathy, viral encephalopathy infantile, near drowning, anoxic brain injury, traumatic head injury, traumatic cardiac arrest, ischemic-hypoxic encephalopathy in newborns, Hepatic encephalopathy, bacterial meningitis, heart failure, postoperative tachycardia, or adult respiratory distress syndrome (ARDS).

At least one aspect of the present technology provides one or more methods for treating myocardial infarction, seizures, traumatic brain injury, or ARDS. The methods comprise inducing mild therapeutic hypothermia in a patient. Mild therapeutic hypothermia can be induced by esophageal cooling. The patient can be kept in a hypothermic state for at least about two hours, for example. The methods may further comprise monitoring at least one physiological parameter of the patient, such as body temperature. The methods may further comprise maintaining the patient's body temperature below about 34 ° C.

At least one aspect of the present technology provides one or more methods for treating myocardial infarction, seizures, traumatic brain injury, or ARDS. The methods comprise inserting a heat transfer device, including a fluid path defined by a fluid inlet lumen and a fluid outlet lumen, into the esophagus of a patient; initiating the flow of a cooling medium along the fluid path; and circulating the cooling medium along the fluid path for a time sufficient to induce systemic hypothermia in the patient.

At least one aspect of the present technology provides one or more methods for treating cardiac arrest. Methods include inducing systemic hypothermia by cooling the esophagus. The methods may further comprise inserting a heat transfer device, including a fluid path defined by a fluid inlet lumen and a fluid outlet lumen, into the esophagus of a patient; initiating the flow of a cooling medium along the fluid path; and circulating the cooling medium along the fluid path for a time sufficient to induce systemic hypothermia in the patient.

At least one aspect of the present technology provides one or more methods for operating temperature management. The methods comprise controlling a patient's core body temperature by esophageal cooling. The methods may further comprise inserting a heat transfer device, including a fluid path defined by a fluid inlet lumen and a fluid outlet lumen, into the esophagus of a patient; initiating the flow of a heat transfer medium along the fluid path; and circulating the heat transfer medium along the fluid path for a time sufficient to control the core body temperature of the patient.

At least one aspect of the present technology provides one or more devices for cooling or heating at least a portion of a patient's body. The devices comprise a heat transfer device that includes a proximal end, a distal end, and at least one flexible tube that extends at the proximal and distal ends. The proximal end includes a heat transfer medium inlet port and a heat transfer medium outlet port. The distal end is configured for insertion into a hole in a patient. The flexible tube defines a fluid inlet lumen and a fluid outlet lumen and the lumens can be configured

ES 2 575 302 T3 to provide a fluid path for the flow of a heat transfer medium. The devices further comprise a supply line connected to the inlet port and a return line connected to the outlet port.

The device can be used to treat or prevent, for example, injury caused by an ischemic condition; ischemia-reperfusion injury; neurological injury; heart injury. The device can be used to treat patients who have had or are suffering from myocardial infarction; attacks; traumatic brain injury; or ARDS. Methods of treating or preventing said conditions or diseases comprise inserting the distal end of the heat transfer device nasal or orally; advancing the distal end into the esophagus of the patient; initiating the flow of a cooling medium along the fluid path; and circulating the cooling medium along the fluid path for a time sufficient to induce systemic hypothermia in the patient. The patient can be kept in a hypothermic state for at least two hours. The methods may further comprise monitoring at least one physiological parameter of the patient, such as body temperature. The methods may further comprise maintaining the patient's body temperature below about 34 ° C.

The device can be used to monitor a patient's core body temperature during, for example, surgical procedures. Methods of controlling the patient's core body temperature comprise inserting the distal end of the heat transfer device nasal or orally; advancing the distal end into the esophagus of the patient; initiating the flow of a heat transfer medium along the fluid path; and circulating the heat transfer medium along the fluid path for a time sufficient to induce control core body temperature in the patient. The subject's core body temperature can be monitored for at least about two hours, for example. The methods may further comprise monitoring at least one physiological parameter of the subject, such as body temperature. The methods may further comprise maintaining the patient's body temperature, for example, below about 34 ° C, between about 34 ° C and about 37 ° C, or about 37 ° C.

At least one aspect of the present technology provides an esophageal heat transfer device comprising (a) a plurality of lumens configured to provide a fluid path for the flow of a heat transfer medium; (b) a heat transfer region configured to contact the esophageal epithelium of a patient; (c) a proximal end including an inlet port and an outlet port; and (d) a distal end configured for insertion into a patient's esophagus. The heat transfer device may further comprise a hollow tube having a distal end configured to extend into the stomach of the patient. The heat transfer device may be capable of contacting essentially the entire esophageal epithelium of the patient. The heat transfer device can comprise a semi-rigid material. The heat transfer device may be capable of cooling at a rate of about 1.2 ° C / h to about 1.8 ° C / hr. The heat transfer device according to the invention is capable of cooling a mass at a speed of approximately 350 kJ / h to approximately 530 kJ / h, and, in particular, at a speed of approximately 430 kJ / h. The heat transfer device according to the invention includes a heat transfer region with a surface area of ​​at least about 100 cm² and, in particular, a surface area of ​​about 140 cm².

At least one aspect of the present technology provides a system for cooling or heating at least a portion of a patient's body, comprising a heat transfer device that includes a proximal end, a distal end, and at least one semi-rigid tube that extends between the proximal and distal ends; a supply line; and a return line. The proximal end of the heat transfer device includes a heat transfer medium inlet port and a heat transfer medium outlet port. The distal end of the heat transfer device is configured for insertion into a hole in a patient, such as the esophageal lumen. The semi-rigid tube defines a fluid inlet lumen and a fluid outlet lumen and the lumens are configured to provide a fluid path for the flow of a heat transfer medium. The supply line connects to the inlet port and the return line connects to the outlet port. The heat transfer device may further comprise a hollow tube having a distal end configured to extend into the stomach of the patient. The heat transfer device may be capable of contacting essentially the entire esophageal epithelium of the patient. The heat transfer device can comprise a semi-rigid material. The heat transfer device may be capable of cooling at a rate of about 1.2 ° C / h to about 1.8 ° C / hr. The heat transfer device may be capable of cooling a mass at a speed of about 350 kJ / h to about 530 kJ / h, and, in particular, at a speed of about 430 kJ / h. The heat transfer device can include a heat transfer region with a surface area of ​​at least about 100 cm² and, in particular, a surface area of ​​about 140 cm².

At least one aspect of the present technology provides a system for monitoring a subject's core body temperature, comprising a heat transfer tube that can be inserted into the subject's esophagus; an external heat exchanger containing a heat transfer fluid; a pump for flowing the heat transfer fluid through a circuit within the heat transfer tube; a heat transfer element in contact with the external heat exchanger; a sensor to detect a parameter and

ES 2 575 302 T3 generating a signal representative of the parameter, wherein the signal is transmitted to a microprocessor to control (i) the flow of the heat transfer fluid within the circuit or (ii) the temperature of the heat transfer fluid. The tube is configured to contact the epithelial lining of the subject's esophagus. The sensor can be a temperature sensor positioned distal to the heat transfer tube and configured to generate a signal representing the subject's core body temperature. The microprocessor can receive input from the target temperature and respond to the signal from the temperature sensor with an integrated proportional differential response to control the rate at which the subject approaches the target temperature. The sensor can be a bubble detector and configured to generate a signal that represents the presence of air in the circuit. The heat transfer device may further comprise a hollow tube having a distal end configured to extend into the stomach of the patient. The heat transfer device may be capable of contacting essentially the entire esophageal epithelium of the patient. The heat transfer device can comprise a semi-rigid material. The heat transfer device may be capable of cooling at a rate of about 1.2 ° C / h to about 1.8 ° C / hr. The heat transfer device according to the invention is capable of cooling a mass at a speed of about 350 kJ / h to about 530 kJ / h, and, in particular, at a speed of about 430 kJ / h. The heat transfer device according to the invention includes a heat transfer region with a surface area of ​​at least about 100 cm² and, in particular, a surface area of ​​about 140 cm²

Brief description of various views of the drawings

Figure 1 is a schematic view of a heat transfer system in accordance with an illustrative embodiment of the present technology.

Figure 2 depicts a heat transfer device in accordance with an illustrative embodiment of the present technology.

Figure 3 shows a schematic view (Figure 3A), from top to bottom (Figure 3B), and in cross section (Figure 3C) of a heat transfer device according to an illustrative embodiment of the present technology.

Figure 4 shows a schematic view of a proximal end of a heat transfer device in accordance with an illustrative embodiment of the present technology.

Figure 5 shows a schematic view (Figure 5A) and various cross-sectional views (Figures 5B-5F) of a distal end of a heat transfer device in accordance with an illustrative embodiment of the present technology.

Figure 6 is a schematic diagram of a distal end of a heat transfer device in accordance with an illustrative embodiment of the present technology.

Figure 7 is a graph depicting the cooling achieved with an illustrative cooling device in accordance with one embodiment of the present technology.

Figure 8 is a graphed comparison of the cooling rate achieved by a heat transfer device of the present technology compared to the cooling rate shown in US Patent Application Publication 2004/0210281 by Dzeng et al. .

Figure 9 is a graph showing the total amount of heat transferred during the heating and holding phase of the experiment.

Detailed description of the invention

The present technology provides relatively non-invasive devices and methods for heating or cooling the entire body of a patient. The present technology further provides devices and methods for treating ischemic conditions by inducing therapeutic hypothermia. Another aspect of the present technology provides devices and methods for inducing therapeutic hypothermia by esophageal cooling. The present application demonstrates that the heat transfer devices and methods of the present technology unexpectedly achieve higher rates of temperature change compared to other devices and methods and, in particular, those mentioned in the publication of the patent application of United States 2004/0210281 by Dzeng et al.

The present technology provides devices and methods for treating patients suffering from various diseases and disorders by inducing mild therapeutic hypothermia (target temperature: approximately 32 ° C to approximately 34 ° C) and by maintaining normothermia (target temperature: approximately 37 ° C). ). In particular, mild therapeutic hypothermia can be induced to treat patients suffering from ischemia or conditions related to ischemia. Without being tied to a particular theory, it is believed that various

ES 2 575 302 T3 molecular and physiological responses associated with the ischemia-reperfusion cascade, including, for example, glutamate release, blood-brain barrier stabilization, oxygen radical production, intracellular signal conduction, protein synthesis, ischemic depolarization, reduced brain metabolism, membrane stabilization, inflammation, activation of protein kinases, cytoskeleton disruption, and early gene expression, they are sensitive to intraischemic and post-ischemic temperature reductions. In particular, mild therapeutic hypothermia can minimize the formation of various metabolic mediators such as free radicals and suppress the inflammatory response associated with ischemia-reperfusion. In addition, with regard to neurological outcomes, mild therapeutic hypothermia can mitigate the pro-inflammatory brain response, decrease the production of excitatory mediators of brain lesions, such as excitatory amino acids and monoamines, decrease brain metabolic rate, and decrease intracranial pressure. . On the other hand, inadvertent hypothermia during surgical procedures can reduce platelet function, impair the enzymes of the coagulation cascade, enhance the effects of anesthetic medications, contribute to coagulopathy, increase cardiac demand, and increase the incidence of infections. of surgical wounds.

Certain modalities of the present technology provide devices and methods for inducing mild therapeutic hypothermia to treat individuals who have suffered from myocardial infarction, seizures, traumatic brain injury, ARDS, hemorrhagic shock, subarachnoid hemorrhage (SAH), including non-traumatic aneurysmal SAH. , neonatal encephalopathy, perinatal asphyxia (hypoxic ischemic encephalopathy), spinal cord injury, meningitis, be about to hang and be about to drown. Without being bound by any particular theory, it is believed that mild therapeutic hypothermia can prevent, reduce, or ameliorate neurological or other injuries associated with the conditions mentioned above. Additional embodiments of the present technology provide devices and methods for inducing mild therapeutic hypothermia to treat individuals who have suffered from metabolic acidosis, pancreatitis, malignant hyperthermia, liver failure, and hepatic encephalopathy. Additional embodiments of the present technology provide devices and methods for controlling the patient's temperature during any general surgical procedure. As used herein, the term "controlling the patient's temperature" refers to a patient's core body temperature and includes reducing core body temperature, maintaining core body temperature, raising core body temperature, inducing hypothermia, maintaining normothermia, and induce hyperthermia.

Certain modalities of the present technology provide control of the patient's temperature by heating or cooling the esophagus. As an example, a heat transfer agent can circulate through a heat transfer device placed in the esophagus of the patient. In certain embodiments, the heat transfer portion of the device is limited to the esophagus of the patient. In certain embodiments, the heat transfer device is in contact with essentially the entire epithelial surface of the patient's esophagus. The heat transfer device may include a partially inflatable balloon or lumen. Alternatively, and in accordance with the present invention, the heat transfer portion of the heat transfer device does not include a balloon or a partially inflatable lumen.

In operation, heat can be transferred to the esophagus from the heat transfer agent, resulting in an increase in the temperature of the esophagus, as well as adjacent organs or structures, including the aorta, right atrium, vena cava , and azygos vein, and lastly, systemic normothermia, or heat can be transferred from the esophagus to the heat transfer agent, resulting in a decrease in the temperature of the esophagus, as well as adjacent organs or structures, including the aorta, right atrium, vena cava, and azygos vein, and lastly, systemic hypothermia.

Certain other modalities of the present technology provide control of the patient's temperature by esophagogastric heat transfer. As an example, a heat exchange medium can flow through a heat transfer device of sufficient length so that the heat transfer portion of the device extends from the patient's esophagus to the patient's stomach. In certain embodiments, the heat transfer device is in contact with essentially the entire epithelial surface of the patient's esophagus. The heat transfer device may include a partially inflatable balloon or lumen. Alternatively, and in accordance with the present invention, the heat transfer portion of the device does not include a balloon or a partially inflatable lumen. Using such an esophagogastric temperature control device to modulate the patient's temperature provides a greater surface area for heat transfer thereby resulting in more efficient and faster temperature management.

Certain modalities of the present technology contemplate inducing mild therapeutic hypothermia by, for example, esophageal cooling, to treat individuals who have suffered cardiac arrest, including cocaine-induced cardiac arrest, traumatic cardiac arrest, and cardiac arrest due to non-causes. coronary.

Still other modalities of the present technology provide control of the patient's temperature by cooling or heating the bladder, colon, rectum, or other anatomical structure of a patient. As an example, a heat exchange medium can circulate through a heat transfer device placed in the bladder, colon, rectum, or other anatomical structure of the patient.

Certain embodiments of the present technology provide a heat transfer system for heating or

ES 2 575 302 T3 cooling a patient. The heat transfer system may include a heat transfer device, a heat exchanger, a heat transfer medium, and a network of tubular structures for the circulation of the heat transfer medium between the heat transfer device and the heat exchanger. In other embodiments, the heat transfer system includes a heat transfer device, a cooler, a refrigerant, and a network of tubular structures for circulating the refrigerant between the heat transfer device and the cooler. In still other embodiments, the heat transfer system can be used to cool and subsequently rewarm the patient, as well as to maintain the patient at a predetermined stable temperature.

In certain embodiments of the present technology, the heat transfer device comprises a distal end, a proximal end, and one or more lengths of tubes extending between them. The proximal end of the heat transfer device includes an inlet port to receive a heat transfer medium from the heat exchanger and an outlet port that allows the heat transfer medium to return to the heat exchanger. Tubes extending approximately from the proximal end of the heat transfer device to approximately the distal end of the heat transfer device may include a heat transfer medium supply tube and a heat transfer medium return tube. The heat transfer medium supply pipe and the heat transfer medium return pipe can be arranged, for example, in parallel or concentrically. The lumens of the heat transfer medium supply tube and the heat transfer medium return tube may be in continuous communication such that the heat transfer medium can flow along a fluid path defined by the lumens of heat transfer medium supply tube and heat transfer medium return tube.

The wall thickness of the heat transfer medium supply tube and / or the heat transfer medium return tube contributes to the heat transfer resistance of the device. Therefore, in certain embodiments, it is preferred that the heat transfer medium supply tube and / or the heat transfer medium return tube have thin walls. For example, the wall of the heat transfer medium supply tube and / or the heat transfer medium return tube may be less than about 1 millimeter. Alternatively, the wall of the heat transfer medium supply tube and / or the heat transfer medium return tube may be less than about 0.01 millimeter. In some embodiments, the wall of the heat transfer medium supply tube and / or the heat transfer medium return tube may be less than about 0.008 millimeters. As will be appreciated by one of ordinary skill in the art, the wall thickness of the heat transfer medium supply tube and / or the heat transfer medium return tube can be varied in increments of about 0.001 millimeters, about 0, 01 millimeters, or about 0.1 millimeters, for example.

The manufacture of heat transfer devices of the present technology is relatively inexpensive. For example, an esophageal heat transfer device can be constructed with the use of an elastomer such as biomedical grade extruded silicone rubber, and an adhesive. Commercially available elastomers and adhesives include, for example, Dow Corning Q7 4765 and Nusil Med2-4213 silicone. The low cost and ease of use of such materials are expected to lead to the widespread adoption of esophageal heat transfer devices of the present technology.

In certain embodiments, the heat transfer device, including, for example, the delivery tube, may comprise a semi-rigid material, such as a semi-rigid plastic, including ethylene tetrafluoroethylene (ETFE), polytetrafluoroethylene (PTFE), perfluoroalkoxy (PFA). ), and fluorinated ethylene propylene (FEP), or a semi-rigid elastomer, such as silicone. A heat transfer device comprising a delivery tube constructed of a semi-rigid material is easier to place in the esophagus of a patient than, for example, a flexible balloon-type device. In particular, a heat transfer device comprising a flexible material, such as a balloon, requires a delivery device, such as a catheter, guide wire, or sleeve, to direct the heat transfer device into the body. esophagus of the patient. Furthermore, a flexible and expandable material such as a balloon is susceptible to failure, such as breaking, cracking, or puncturing. The use of a semi-rigid material in the construction of a heat transfer device reduces the points of failure associated with the balloon-type device.

In certain embodiments a rigid sleeve can be used to guide the heat transfer device during placement on a patient. The rigid sleeve may have a cross section such that the sleeve comprises approximately a semicircle in cross section. The sleeve can be removed by sliding proximally from the heat transfer device. Such a sleeve has certain benefits compared to a centrally placed guidewire, including a reduced rate of complications when using a guidewire, such as loss of the guidewire in the body cavity and damage from the guidewire itself. .

An esophageal heat transfer device of the present technology is portable, relatively easy to use, and can be inserted into the esophagus of a patient by a single healthcare provider, including a nurse, trained first aid personnel, a paramedic, emergency medical technician assistant, or

ES 2 575 302 T3 another pre-hospital or hospital care provider. An esophageal heat transfer device of the present technology has advantages over devices that require multiple people and / or a person trained in advanced medical care. Additionally, in a surgical setting, for example, an esophageal heat transfer device of the present technology has advantages over other temperature management modalities in that less staff and attention are required to insert, use, and / or monitor a device. esophageal heat transfer.

For example, users of a balloon-type device should be aware of over-inflation or under-inflation of the balloon. Over inflation can lead to unwanted results, including compression necrosis. Under inflation can reduce the device's ability to transfer heat to / from the patient. The use of a balloon-type heat transfer device may also require the use of a pressure monitor to monitor inflation pressure. Even when used in conjunction with a pressure monitor, it may not be able to achieve proper balloon inflation.

The heat transfer device can be, for example, a pharyngoesophageal heat transfer device, an esophageal heat transfer device, an esophagogastric heat transfer device, or a pharyngeal-esophageal-gastric heat transfer device. For example, an esophageal heat transfer device may include a heat transfer region of approximately twenty (20) centimeters. Alternatively, an esophageal-gastric heat transfer device may include a heat transfer region of approximately forty (40) centimeters. In yet another alternative, a pharyngeal-esophagus-gastric heat transfer device may include a heat transfer region of about forty-five (45) to about fifty (50) centimeters. The heat transfer devices of the present technology can include heat transfer regions of about 22, about 24, about 26, about 28, about 30, about 32, about 34, about 36, about 38, about 40, about 42, about 44, about 46, about 48, about 50, about 52, about 54, about 56, about 58, about 60, about 62, about 64, about 66, about 68 or about 70 centimeters.

The heat transfer devices of the present technology can have a heat transfer region that has a diameter of, for example, about 1.0 to about 2.0 centimeters. The diameter of the heat transfer region can be about 1.1, about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about 1, 8, or about 1.9 centimeters. In certain embodiments, a heat transfer region of a heat transfer device of the present technology has a length of approximately 32 centimeters and a diameter of approximately 1.4 centimeters, giving a surface area of ​​approximately 140 cm.².

Increasing the length and / or circumference of the device's heat transfer region, and therefore the surface area of ​​the heat transfer region, improves the efficiency and rate at which the patient is warmed or cooled (or warms up again). In certain embodiments the heat transfer region can be approximately^{2 2 22} approximately approximately approximately approximately approximately approximately approximately approximately heat transfer region can contact essentially the entire epithelial surface of a subject's esophagus.

inches², about 20 inches², about 25 inches², 30 inches²,

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120

160

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The heat transfer device can be adapted to allow gastric access to the patient's healthcare provider. The heat transfer device may incorporate, for example, a gastric tube or a gastric tube. The gastric tube or gastric tube may be parallel to the heat transfer medium supply tube and the heat transfer medium return tube. Alternatively, the gastric tube, the gastric tube, or both may be in a concentric arrangement with at least one of the heat transfer medium supply tube or the heat transfer medium return tube. The gastric tube can be, for example, a temperature tube.

Another embodiment of the present technology provides a multi-lumen heat transfer device for inducing mild therapeutic hypothermia. The heat transfer device can include one or more lumens that provide a fluid path for the circulation of a refrigerant. For example, the heat transfer device may include a refrigerant supply pipe and a refrigerant return pipe. The

ES 2 575 302 T3 lumens of the refrigerant supply pipe and the refrigerant return pipe may be in continuous communication with each other to define a fluid path for the refrigerant flow. The refrigerant supply pipe and the refrigerant return pipe can be arranged, for example, in parallel or concentrically.

Another embodiment of the present technology provides a multi-lumen heat transfer device for controlling the temperature of the patient. The heat transfer device may include one or more lumens that provide a fluid path for the circulation of a heat transfer medium. For example, the heat transfer device may include a medium supply tube and a medium return tube. The lumens of the medium supply tube and the medium return tube may be in continuous communication with each other to define a fluid path for the flow of the medium. The medium supply tube and the medium return tube can be arranged, for example, in parallel or concentrically.

Certain embodiments of the present technology may use a controller such as that described in US20070203552 (Machold). In particular, a controller can use a proportional integral derivative (PID) cascade control scheme. In such a scheme, a control system is provided which can be divided into two sections: (a) a control section of a PID Bulk that gets input from the healthcare provider or other user, such as the target temperature, and inputting the sensors into the patient representing the temperature of the patient, and calculating an intermediate reference temperature (SP1) and an output signal to the PID control of the Heat Transfer Fluid; and (b) the PID control of the Heat Transfer Fluid, which receives an input from the control section of the PID Bulk and from a sensor that represents the temperature of a heat transfer fluid, and generates a signal that controls the temperature. of the heat exchanger by, for example, varying the energy input to the heat exchanger.

The heat transfer fluid circulates in the heat exchanger, so that the PID of the Heat Transfer Fluid essentially controls the temperature of the heat transfer fluid. In this way, the control scheme can automatically achieve a specific goal based on input from sensors placed on the patient and the logic built into the controller. Additionally, this scheme allows the unit to automatically modify the patient's temperature very gradually over the last tenths of a degree to achieve the target temperature very carefully and avoid dramatically and potentially overshooting or damaging the changes in the electronic power supply to the exchanger. of heat. Once the target temperature is achieved, the system continues to operate automatically to add or remove heat at exactly the rate necessary to keep the patient at the target temperature.

In general, the controller can include a control variable, such as the pump output or the energy input to the heat exchanger. A sensor or sensing unit can function as a feedback device to detect a parameter, such as patient temperature or the presence of air in a line, and generate a feedback signal related to the control variable. The control unit executes a PID operation, in which the control variable is adjusted according to the comparison between the feedback signal and a predetermined target value.

As an example, the feedback signal T may represent the patient's temperature and the predetermined target value TObj may represent a target temperature set by a healthcare professional. When the feedback signal T is greater than the target value TObj, this means that the patient's temperature is too high. Consequently the controller, for example, increases or decreases the pump output or the energy input to the heat exchanger to change the temperature and / or the flow rate of the heat exchange medium. When the feedback signal T is less than the target value TObj, this means that the patient's temperature is too low. Consequently the controller, for example, increases or decreases the pump output or the energy input to the heat exchanger to change the temperature and / or the flow rate of the heat exchange medium.

Certain embodiments of the present technology provide an unexpectedly higher rate of temperature change relative to other devices and methods. The present methods and devices can provide a cooling rate of from about 0.5 ° C / hour to about 2.2 ° C / hour in a large animal model similar in size to an average adult human. The present methods and devices are capable of demonstrating a total heat removal capacity from about 250 kJ / hour to about 750 kJ / hour. For example, the present methods and devices can provide a cooling rate of from about 1.2 ° C / hour to about 1.8 ° C / hour in a large animal model similar in size to an average adult human, demonstrating a total heat removal capacity from about 350 kJ / hour to about 530 kJ / hour. The methods and devices of the present technology can provide a cooling rate of about 1.3, about 1.4, about 1.5, about 1.6, and about 1.7 ° C / hour. The methods and devices of the present technology are capable of demonstrating a total heat removal capacity of about 350, about 360, about 370, about 380, about 390, about 400, about 410, about 420, about 430, about 440, about 450, about 460, about 470, about 480, about 490, about 500, about 510, and approximately 520 kJ / hour.

ES 2 575 302 T3

While not wishing to be bound by any particular theory, it is believed that the methods and devices of the present technology transfer more heat per unit time than other devices. For example, the heat transfer devices of the present technology include heat transfer regions that, for example, extend essentially the entire length and / or circumference of the patient's esophagus, providing a greater surface area of ​​contact between the heat transfer region of the heat transfer device and the anatomy of the patient including the esophageal epithelium and the vasculature surrounding the esophagus. The heat transfer devices of the present technology further allow the reduction of gastric pressure through gastric ventilation, thereby reducing the possibility of the esophageal mucosa swelling and distension away from contact with the esophageal mucosa, and further improves heat transfer through the esophageal mucosa. Additionally, materials for constructing the heat transfer devices of the present technology include those with superior heat transfer characteristics. The heat transfer devices of the present technology can be manufactured with thinner wall thicknesses, which further reduces the resistance to heat transfer through the device and increases the effectiveness of removing heat from, or adding heat to. , the patient.

The technology described herein will now be described with respect to the accompanying figures; however, the scope of the present technology is not intended to be limited by them. It should be understood that the scope of the present technology will not be limited to the specific embodiments described in the present description. The technology may be practiced differently than is particularly described and still be within the scope of the claims.

Figure 1 is a schematic view of a heat transfer system 100 in accordance with one embodiment of the present technology. The heat transfer system 100 includes a heat transfer device 102, a heat exchanger 104, a heat transfer medium 106, and a network of tubular structures 108 for the circulation of the heat transfer medium 106 between the device. heat transfer system 102 and heat exchanger 104.

Heat exchanger 104 is configured to heat or cool heat transfer medium 106. Heat exchanger 104 can be any of a variety of conventionally designed heat exchangers 104. For example heat exchanger 104 can be a standard cooler, such as an RF-25 Cooling Recirculator manufactured by New Brunswick Scientific. The heat transfer medium 106 can be a gas, such as, for example, nitrous oxide, freon, carbon dioxide, or nitrogen. Alternatively, the heat transfer medium 106 can be a liquid, such as, for example, water, saline, propylene glycol, ethylene glycol, or mixtures of these. In other embodiments, the heat transfer medium 106 can be an aqueous suspension, such as, for example, a mixture of ice and salt. In still other embodiments, the heat transfer medium 106 may be a gel, such as, for example, a cooling gel. Alternatively, the heat transfer medium 106 can be a solid, such as, for example, ice or a heat conducting metal. In other embodiments, the heat transfer medium 106 can be formed, for example, by mixing a powder with a liquid. Therefore, it should be understood that combinations and / or mixtures of the aforementioned media can be used to achieve a heat transfer medium 106 in accordance with the present technology.

The network of tubular structures 108 for the circulation of the heat transfer medium 106 may include an external supply tube 110 and an external return tube 112. The external supply tube 110 defines an external supply lumen 114 that provides a path of fluid for the flow of heat transfer medium 106 from heat exchanger 104 to heat transfer device 102. External return tube 112 defines an external return lumen 116 that provides a fluid path for the flow of heat transfer medium 106 from heat transfer device 102 to heat exchanger 104. A pump 118 can be used to circulate the heat transfer medium 106 through the network of tubular structures 108, and the flow rate of the medium, and therefore the heat transfer capabilities of the device, can be regulated by the adjust pumping speed.

The heat transfer device 102 is adapted to be positioned within an anatomical structure of a mammalian patient. The heat transfer device 102 has a proximal and a distal end. The distal end of the heat transfer device 102 can be configured to insert into a hole in the body. For example, the distal end of the heat transfer device 102 can be configured to insert into the nostrils, mouth, anus, or urethra of a patient. When properly inserted, the distal end of the heat transfer device 102 can be ultimately positioned in the esophagus, rectum, colon, bladder, or other anatomical structure. The proximal end of heat transfer device 102 includes an inlet port 120 and an outlet port 122. The inlet port 120 and the outlet port 122 connect to the network of tubular structures 108 for circulation of the heat transfer medium 106. For example, the inlet port 120 can be connected to the external supply tube 110 and the port outlet 122 can be connected to external return tube 112. Thus, in certain embodiments, the heat exchanger 104 may be in continuous communication with the heat transfer device 102 via the network of tubular structures 108.

In operation, the heat transfer device 102 is positioned on an anatomical structure, such as the

ES 2 575 302 T3 esophagus. Heat exchanger 104 is used to heat or cool heat transfer medium 106 which is supplied to heat transfer device 102 via external supply tube 110. Heat transfer medium 106 flows through supply tube external 110 and enters heat transfer device 102 through inlet port 120. Heat transfer medium 106 circulates through heat transfer device 102 and exits heat transfer device 102 through outlet port 122, and returns to heat exchanger 104 via external return tube 112. Raise or lowering the temperature of the heat transfer medium 106 modifies the patient's body temperature.

The heat transfer system 100 may further incorporate a device that measures a physiological parameter such as temperature, pressure, or electromagnetic fluctuations. For example, heat transfer system 100 may include one or more thermometers 124, each with one or more temperature probes 126, to measure ambient temperature, patient temperature, or temperature of heat transfer medium 106. . The thermometers can be separate devices or integrated into the heat transfer system 100.

Figure 2 depicts a heat transfer device 200 in accordance with one embodiment of the present technology. For the purposes of further clarifying this embodiment, the heat exchanger will be referred to as a cooler (not shown) and the heat transfer medium will be referred to as a refrigerant. However, it should be understood that any suitable heat exchanger and any suitable heat transfer medium can be used with the heat transfer device depicted in Figure 2.

The heat transfer device 200 comprises a distal end 202, a proximal end 204, and a length of flexible tubes 206 extending between them. Proximal end 202 includes an inlet port 208 to receive refrigerant from the cooler and an outlet port 210 that allows refrigerant to return to the cooler.

Inlet port 208 comprises a standard plumbing tee fitting 212. Alternatively, any fitting with two or more open ends, such as a star fitting, may be used. The splice can be composed of any suitable material, including, for example, metals, such as, copper or iron; metal alloys, such as steel or brass; or plastics, such as polyvinyl chloride (PVC) or polyethylene (PE). A brass plug 214 is attached to the open proximal end of the T-tube fitting 212. Alternatively, standard caps, such as metal or plastic caps, can be attached to the open proximal end of the fitting. Cap 214 includes an opening to allow clearing of the tubes. Plug 214 is attached to the joint with chemical sealant 216, such as, for example, Room Temperature Vulcanizing (RTV) Silicone Sealant. In other embodiments, the inlet port 208 can be manufactured in a way that eliminates the need for fixed end caps, such as, for example, by extrusion.

The outlet port 210 comprises a standard plumbing tee fitting 212. Alternatively, any fitting with two or more open ends, such as a star fitting, may be used. The splice can be composed of any suitable material, including, for example, metals, such as copper or iron; metal alloys, such as steel or brass; or plastics, such as PVC or PE. Brass plugs 214 attach to the open proximal end and open distal end of the T-tube fitting. Alternatively, standard caps, such as metal, metal alloy, or plastic caps, can be attached to the open ends of the fitting. Each plug 214 may include an opening to allow clearing of the tubes. Plugs 214 are attached to the joint with chemical sealant 216, such as, for example, RTV Silicone Sealant. In other embodiments, the outlet port 210 can be manufactured in a way that eliminates the need for fixed end caps, such as, for example, by extrusion.

The length of tubes 206 extending between proximal end 204 and distal end 202 of heat transfer device 200 is a coolant supply tube 218. Coolant supply tube 218 may be comprised of transparent vinyl. Alternatively, the refrigerant supply tube 218 may be comprised of other suitable materials, such as, for example, medical grade clear flexible PVC. The dimensions of the refrigerant supply tube 218 can be approximately 0.625 OD x 0.500 ID. Refrigerant supply tube 218 is attached to inlet port 208 with chemical sealant 216, such as, for example, RTV Silicone Sealant. Coolant supply tube 218 extends from inlet port 208 to distal end 202 of heat transfer device 200. The length of the refrigerant supply tube 218 can be from about eighteen (18) to about fifty-two (52) centimeters. In certain embodiments, the length of the refrigerant supply tube 218 can be from about eighteen (18) to about twenty-two (22) centimeters. In certain embodiments, the length of the refrigerant supply tube 218 may be from about thirty (30) to about forty-two (42) centimeters. In other embodiments, the length of the refrigerant supply tube 218 may be from about forty-five (45) to about fifty-two (52) centimeters. The length of the refrigerant supply tube 218 may be approximately thirty-two (32) centimeters.

The distal end 202 of the heat transfer device 200 includes an end cap 220. The end cap 220 can be comprised of any suitable material, including, for example, metals, such as,

ES 2 575 302 T3 copper or iron; metal alloys, such as steel or brass; or plastics, such as PVC or PE. End cap 220 is attached to the refrigerant supply tube with chemical sealant 216, such as, for example, RTV Silicone Sealant.

A refrigerant return tube 222 may be positioned within the refrigerant supply tube 218. The refrigerant return tube 222 may be comprised of clear vinyl. Alternatively, the refrigerant return tube 222 may be comprised of other suitable materials, such as, for example, medical grade clear flexible PVC. The outside diameter of the refrigerant return tube 222 is smaller than the inside diameter of the refrigerant supply tube 218. For example, the dimensions of the refrigerant return tube 222 may be approximately 0.437 OD x 0.312 OD. inside diameter (ID). The refrigerant return tube 222 can be attached to one or both of the inlet port 208 or the outlet port 210 with chemical sealant 216, such as, for example, RTV Silicone Sealant.

The refrigerant return tube 222 does not extend to the end cap 220 at the distal end 202 of the heat transfer device 200. Therefore, the refrigerant supply tube lumen 224 and the refrigerant return tube lumen Refrigerant 226 may be in continuous communication with each other, thereby defining a fluid path for refrigerant flow.

In operation, the refrigerant enters the inlet port 208 and flows through the lumen of the refrigerant supply tube 224 to the distal end 202 of the heat transfer device 200, which can be placed in, for example, the esophagus of a patient. . The refrigerant then flows through the lumen of the refrigerant return tube 226 to the outlet port 210. In operation, heat is transferred, for example, from the esophagus to the coolant, resulting in a decrease in the temperature of the esophagus, as well as the adjacent organs, and finally, systemic hypothermia.

In certain embodiments, additives with a high heat transfer coefficient, such as copper, for example, can be added to the material used to make the refrigerant supply tube 218 or the refrigerant return tube 222. In one embodiment, the lengths Cable, for example, that runs linear or coiled along the length of the tube can be included. In other embodiments, the particulate material with a high heat transfer coefficient may be mixed with the material used to make the refrigerant supply pipe 218 or the refrigerant return pipe 222 (eg, vinyl or pVc) before or during the operation. extrusion.

In certain embodiments, the walls of the refrigerant supply tube 218 and / or the refrigerant return tube 222 can be relatively thin. For example, the wall of the refrigerant supply tube 218 may be less than about 1 millimeter. Alternatively, the wall of the refrigerant supply tube 218 may be less than about 0.01 millimeter. In some embodiments, the wall of the refrigerant supply tube 218 may be less than about 0.008 millimeters. As will be appreciated by one of ordinary skill in the art, the wall thickness of the heat transfer medium supply tube and / or the heat transfer medium return tube can be varied in increments of about 0.001 millimeters, about 0, 01 millimeters, or about 0.1 millimeters, for example.

Optionally, the heat transfer device 200 may include a gastric tube 228, to allow gastric access and, for example, gastric suction as well as gastric lavage for therapeutic and / or diagnostic purposes, if desired. Gastric tube 228 can be comprised of clear vinyl. Alternatively, gastric tube 228 may be comprised of other suitable materials, such as, for example, medical grade clear flexible PVC. The outer diameter of the gastric tube 228 is less than the inner diameter of the refrigerant return tube 222. For example, the dimensions of the gastric tube 228 may be approximately 0.250 outer diameter (OD) x 0.170 inner diameter (ID). Gastric tube 228 can be attached to the most proximal port, either inlet port 208 or outlet port 210, with chemical sealant 216, such as, for example, RTV Silicone Sealant. Gastric tube 228 may allow the patient's healthcare provider to insert, for example, a nasogastric tube that allows suction of gastric contents. Alternatively, gastric tube 228 may allow the patient's healthcare provider to insert, for example, a gastric temperature tube (not shown).

Optionally, an antibiotic or antibacterial coating can be applied to portions of the refrigerant supply tube 218, the refrigerant return tube 222, or the gastric tube 228. Particularly, an antibiotic or antibacterial coating can be applied to portions of the tubes which, with insertion into a patient, they may contact, for example, a lining of the patient's mucosa. For example, topical antibiotics, such as tobramycin, colistin, amphotericin B, or combinations of these, can be applied to the tubes. The incorporation of an antibiotic or antibacterial coating can allow selective decontamination of the digestive tract (DDS), which can further improve the outcome.

As another alternative, all or part of the heat transfer device 200 can be manufactured, for example, by extrusion. Using such a fabrication mode would eliminate the need to seal the joints or fixed end caps and reduce the points at which leaks may exist.

ES 2 575 302 T3

Figure 3 depicts a heat transfer device 300 in accordance with one embodiment of the present technology. The heat transfer device 300 comprises a proximal end 302, a distal end 306, and a length of flexible tubing 304 extending between them.

All or part of the heat transfer device 300 can be manufactured, for example, by extrusion. Using such a fabrication mode would eliminate the need to seal the joints or stationary end caps and reduce the points at which leaks may exist. Alternatively, or in addition, a fast setting adhesive such as RTV silicone sealant or temperature set sealant can be used to seal the joints and / or connect the tubes together. Heat transfer device 300 can be constructed with the use of a biocompatible plastic and / or elastomer, and, optionally, adhesive. For example, biomedical grade extruded silicone rubber such as Dow Corning Q7 4765 silicone, and an adhesive such as Nusil Med2-4213 can be used to make heat transfer device 300.

Figure 3A shows a schematic view of the exterior of the heat transfer device 300. The heat transfer device 300 includes an inlet port 308, a heat transfer medium supply tube 310, a heat transfer medium return tube. heat transfer 312, and an outlet port 314. The heat transfer device further includes a central tube 316 which, for example, allows gastric access. The center tube 316 is in a concentric arrangement with the heat transfer medium supply tube 310 or the heat transfer medium return tube 312 (see Figure 3B). The central tube lumen 318 provides the healthcare professional with access to, for example, the patient's stomach while the heat transfer device is positioned within the patient's esophagus.

Figure 3C is a cross-sectional view along line 3C, which is identified in Figure 3B.

The outermost tube is the heat transfer medium supply tube 310. The heat transfer medium supply tube 310 extends approximately from the inlet port 308 to approximately the distal end 306 of the heat transfer device 300. The length of the heat transfer medium supply tube 310 can be from about eighteen (18) to about seventy-five (75) centimeters. In a particular embodiment, the length of the heat transfer medium supply tube 310 is approximately thirty-two (32) centimeters. The outer diameter of the heat transfer medium supply tube 310 can be, for example, from about 1.0 to about 2.0 centimeters. In a particular embodiment, the outer diameter of the heat transfer medium supply tube 310 is approximately 1.4 centimeters.

With insertion into, for example, a patient's esophagus, the wall of the heat transfer medium supply tube 310 may be in direct contact with the patient's esophagus. As noted above, the length and / or circumference of the heat transfer medium supply tube 310, and thus the surface area of ​​the heat transfer medium supply tube 310, can vary. Increasing the contact area between the heat transfer device 300 and the patient's esophagus improves the efficiency and rate at which the patient cools or warms (or rewarms). In certain embodiments the surface area of ​​the heat transfer medium supply tube 310 can be approximately 50 cm.² about 350 cm². In a particular embodiment, the surface area of ​​the heat transfer region of the heat transfer medium supply tube 310 may be approximately 140 cm.². In certain embodiments, the heat transfer medium supply tube 310 can contact essentially the entire epithelial surface of a patient's esophagus.

Inside the heat transfer medium supply tube 310 is the heat transfer medium return tube 312. The outside diameter of the heat transfer medium return tube 312 is smaller than the inside diameter of the supply tube. heat transfer medium 310. The heat transfer medium return tube 312 does not extend to the distal end of the heat transfer medium supply tube 310. Therefore, the lumen of the heat transfer medium supply tube 320 and the lumen of the heat transfer medium return tube 322 are in continuous communication with each other, thus defining a fluid path for the flow of the medium. heat transfer.

Inside the return tube of the heat transfer medium is the central tube 316. The outer diameter of the central tube 316 is smaller than the internal diameter of the return tube of the heat transfer medium 312. The central tube 316 can be, for example, a gastric tube, to allow gastric access. The central tube 316 allows a healthcare professional to insert, for example, a nasogastric tube that allows suction of gastric contents. Alternatively, central tube 316 allows a healthcare professional to insert, for example, a gastric temperature tube.

The distal end of the heat transfer medium supply tube 310 may be sealed with an end cap 324. The end cap 324 may be constructed of, for example, silicone. End cap 324 may include a hole or other passage through which center tube 316 may pass. Similarly, the proximal end of the heat transfer medium return tube 312 may be sealed with an end cap 326. End cap 326 can be constructed of, for example, silicone. End cap 326 may include one hole or other

ES 2 575 302 T3 passage through which the central tube 316 can pass. The joints between the different components and the tubes can be sealed with a 328 sealant, such as Nusil Med2-4213.

Figure 4 shows various views of a proximal end of a heat transfer device in accordance with the present technology.

The heat transfer device comprises at least two concentrically arranged tubes, such as a heat transfer supply tube 402 and a heat transfer return tube 404, that form a multi-lumen heat transfer device having a lumen configuration generally coaxial. The proximal ends of each of the heat transfer supply tube 402 and the heat transfer return tube 404 can be sealed with end caps (not shown). The heat transfer device optionally includes a first central tube 410 and / or a second central tube 412. For example, the heat transfer device may comprise one or more gastric tubes.

The lumen of heat transfer supply tube 406 ti a diameter sufficient to allow the passage of the heat transfer return tube 404. Likewise, the lumen of the heat transfer return tube 408 may be of a sufficient diameter to allow the passage of the first central tube 410 and / or the second central tube 412. The first central tube 410 and the second central tube 412 can be, for example, gastric tubes that provide access to the stomach of the patient and allow the suction of gastric contents and / or the placement of a gastric temperature tube. The end cap (not shown) of the heat transfer return tube 404 may include a hole or other passage through which the center tubes 410 and 412 pass.

The heat transfer supply tube 402 can be coupled to an inlet port 414. The inlet port 414 can be coupled to an external supply tube (not shown) equipped with standard connectors to connect to a cooling and / or heating device. The heat transfer return tube 404 can be coupled to an outlet port 416. The outlet port 416 can be coupled to an external return tube (not shown) equipped with standard connectors to connect to the cooling and / or heating device.

Figure 5 shows schematic and cross-sectional views of a distal end of a heat transfer device in accordance with the present technology.

The heat transfer device as depicted in Figure 5A comprises at least two concentrically arranged tubes, such as a heat transfer supply tube 502 and a heat transfer return tube 504, to form a heat transfer device. multi-lumen heat that has a generally coaxial lumen configuration. The distal end of the heat transfer supply tube 502 extends beyond the distal end of the heat transfer return tube 504 so that the heat transfer supply tube 502 and the heat transfer return tube 504 they form a heat transfer flow path. The distal end of the heat transfer delivery tube 502 may be rounded or otherwise shaped to facilitate insertion and placement of the heat transfer device in the esophagus of the patient. The heat transfer device may further comprise a first central tube 506 and / or a second central tube 508. The first central tube 506 and the second central tube 508 can be, for example, gastric tubes that provide access to the patient's stomach and allow suction of gastric contents and / or placement of a gastric temperature tube.

Figure 5B is a cross-sectional view along line 5B, which is identified in Figure 5A. The heat transfer supply tube 502 and the heat transfer return tube 504 are arranged concentrically. The heat transfer return tube 504 is positioned within the lumen of the heat transfer supply tube 510. The first core tube 506 and the second core tube 508 are positioned within the lumen of the heat transfer return tube 512. A healthcare professional can, for example, insert a gastric temperature tube (not shown) through of the first lumen of the central tube 514 and / or of the second lumen of the central tube 516.

Figures 5C-5F show cross-sectional views of various alternate configurations of a multi-lumen heat transfer device in accordance with one embodiment of the present technology.

As shown in Figure 5C, the lumen of the heat transfer supply tube 510 and the lumen of the heat transfer return tube 512 can be arranged in parallel with each other. As shown in Figure 5D, the first lumen of the central tube 514 and the second lumen of the central tube 516 can further be arranged in parallel to the lumen of the heat transfer supply tube 510 and the lumen of the heat transfer return tube. 512. Alternatively and as shown in Figures 5E and 5F, the first lumen of the central tube 514 and / or the second lumen of the central tube 516 may be positioned between the lumen of the heat transfer supply tube 510 and the lumen of the return tube. heat transfer device 512. Optionally, a gastric tube or gastric tube may be inserted into the stomach of a patient via the first lumen of the central tube 514 and / or the second lumen of the central tube 516.

The esophageal heat transfer device shown in Figures 2-5 and described earlier in the

ES 2 575 302 T3 present description is merely illustrative and is not intended to limit the present technology. The heat transfer device of the present technology can be configured to be inserted into the nasal passage, mouth, anus, or urethra of a patient. When properly inserted, the heat transfer portion of the device can be placed last in the esophagus, stomach, rectum, colon, bladder, or other anatomical structure.

Figure 6 depicts a schematic view of a distal end of a heat transfer device in accordance with one embodiment of the present technology.

In certain embodiments, an esophageal heat transfer device incorporates a gastric tube 602. Gastric tube 602 may be the central tube of the concentric tube arrangement and may comprise a generally hollow tube that provides gastric access. For example, a tube that allows suction of gastric contents can be inserted into the stomach of the patient via gastric tube 602. In certain embodiments, gastric tube 602 serves as a tube to suction stomach contents and the need to place a separate nasogastric tube is eliminated. As another example, a gastric temperature tube can be inserted through gastric tube 602.

Gastric tube 602 may include various ports 604 that serve as small tubular connections or passages from the external environment (here, the patient's stomach) to the lumen of gastric tube 606. Ports 604 can communicate directly (and only) with the tube lumen gastric 606. Ports 604 may be positioned at the distal end of the heat transfer device to provide additional portals of communication between the patient's stomach and gastric tube 602. Ports 604 provide additional passages for gastric contents to flow out of the patient's stomach through the lumen of gastric tube 606, thereby reducing the likelihood of blockage of the stomach's single lumen of semisolid contents.

In other embodiments, an esophagogastric heat transfer device comprises concentric tubes such that the more centered tube serves as a gastric tube 602. In such an arrangement, the outermost tube may be, for example, a medium delivery tube. heat transfer medium 608. A heat transfer medium return tube 610 may be positioned within the heat transfer medium supply tube 608. Similarly, gastric tube 602 can be placed within heat transfer medium return tube 610.

As shown in Figure 6, the heat transfer device may be an esophageal or esophagus-gastric heat transfer device and comprises three concentrically arranged tubes, including a heat transfer medium supply tube 608, a heat transfer tube return heat transfer medium 610, and a gastric tube 602 to form a multiple lumen heat transfer device having a generally coaxial lumen configuration. The heat transfer portion of the heat transfer device can be confined to the esophagus of the patient, while the gastric tube 602 extends into the stomach of the patient. The heat transfer device may further include ports 604 along the side of gastric tube 602. The distal end of gastric tube 602 includes various ports along the side of the tube to provide access to the lumen of gastric tube 606, thereby reducing the likelihood of blockage of the stomach's single lumen of semisolid contents. The addition of such ports 604 can improve and increase the removal of stomach contents, which, in turn, can improve the contact between the gastric mucosa and the heat transfer device. Such improved contact can increase heat transfer between the heat transfer device and the gastric mucosa.

The port configuration as shown in Figure 6 is oval. However, the ports can be, for example, circular, rectangular, or any other shape that allows the flow of gastric contents from the stomach into the lumen of gastric tube 606.

In certain embodiments, the term "patient" refers to a mammal in need of therapy for a condition, disease, or disorder or the symptoms associated therewith. The term "patient" includes dogs, cats, pigs, cows, sheep, goats, horses, rats, mice, and humans. The term patient does not exclude an individual who is normal in every way.

As used herein, the term "treating" refers to reducing; to prevent; essentially inhibit, delay, or reverse the progression of; essentially improve the clinical and / or non-clinical symptoms of; or essentially preventing or delaying the onset of clinical and non-clinical symptoms of a disease, disorder, or condition.

In the preceding paragraphs, the use of the singular may include the plural except where specifically indicated. As used herein, the words a, an, the, and the mean one or more, unless otherwise specified. Additionally, when aspects of the present technology are described with reference to lists of alternatives, the technology includes any individual member or subset of the list of alternatives and any combination of one or more of these.

The descriptions of all patents and publications, including published patent applications, are incorporated by reference in their entirety to the same extent as if each patent and publication had been specifically and individually incorporated by reference.

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It should be understood that the scope of the present technology will not be limited to the specific modalities described above. The present technology may be practiced differently than is particularly described and still be within the scope of the accompanying claims.

Likewise, the following examples are presented to more fully illustrate the present technology. However, these should not be construed in any way as limiting the broad scope of the technology described herein.

Examples

Example 1: Cooling a Model System

An experiment was conducted to quantify the approximate rate of temperature reduction achievable using an illustrative embodiment of the present technology. The target temperature reduction is 4 ° C. Data was collected and plotted on a common XY chart, as shown in Figure 7.

The arrangement of equipment for this experiment is shown in Figure 1. A brief description of each piece of equipment is as follows:

1. The heat transfer device 102 was an exemplary embodiment of a heat transfer device in accordance with the present technology.

two. An insulated container, 96 cm (l) x 36 cm (w) x 36 cm (h), containing 88 kg of water at the initial temperature shown in Table 1 represented the mass to be cooled.

3. A 110V electric pump, Little Giant Model PES-70 (4.4 l / min free flow) was used to circulate hot water inside the insulated container (2) to maintain the homogeneous temperature of the water inside this container.

Four. Heat exchanger 104 comprised an insulated container, 51cm (l) x 28cm (w) x 34cm (d), containing 40kg ice water.

5. Pump 118 comprised a 110V electric pump, Little Giant Model PES-70 (250 ml / min as installed) and was used to provide circulation of the coolant from heat exchanger 104 through external supply tube 110, then through heat transfer device 102, then through external return tube 112, and back to heat exchanger 104.

6. External supply tube 110 comprised a Watts # SVKI10 clear vinyl, 5/8 (of) x ¹Z (di) x 42 (l), to transport the refrigerant from heat exchanger 104 to heat transfer device 102.

7. The external return tube 112 comprised a Watts # SVKI10 clear vinyl, 5/8 (of) x ¹Z (di) x 42 (l), to transport the refrigerant from the heat transfer device 102 to the heat exchanger 104.

8. A 124 thermometer, such as a waterproof digital thermometer that included 2 remote probes 126, Taylor Model 1441, was used to monitor:

to. the temperature of the refrigerant (T3 as shown in Figure 1) near the discharge of the external return pipe 112 in the heat exchanger 104;

b. ambient temperature (T4 as shown in Figure 1) inside the test cell.

9. A 124 thermometer, such as a waterproof digital thermometer that included 2 remote probes 126, Taylor Model 1441, was used to monitor:

to. the temperature of the hot water (T1 as shown in Figure 1) inside the insulated container (2), at the opposite end of the circulation pump (3).

b. the temperature of the hot water (T2 as shown in Figure 1) inside the insulated container (2), at the end closest to the circulation pump (3).

The body to be cooled in each iteration of this experiment was a water mass of 88 kg, which was kept in an insulated container (2) with measurements of 94 x 36 x 26 cm. This mass was selected as it represents the body mass of a typical adult male. Heat transfer to ambient air by free convection was through the 94 x 36 cm upper surface of the water body. The initial temperature of this body of water for each iteration of the procedure is shown in Table 1.

ES 2 575 302 T3

The coolant for each iteration of this experiment was a 30 kg body of water containing an additional 10 kg of ice, which was kept in an insulated container. The ice was used to keep the coolant temperature nearly constant for the duration of each iteration of the experiment without the need for a powered cooler, and was replenished at the start of each iteration for which conductive cooling mode was enabled.

There are two modes of temperature reduction to consider in this experiment. These are convective cooling to ambient air, and conductive cooling through the heat transfer device. To quantify the contribution of each mode to the total reduction in temperature, a control case was run with the conductive cooling mode disabled (no refrigerant circulated through the heat transfer device). The procedure was then run two additional times with the conductive cooling mode enabled (the heat transfer device was immersed in the hot water body, and the coolant was circulated through it). The difference between the rates of temperature reduction, with and without conductive cooling enabled, is the rate of temperature reduction due to conductive cooling through the heat transfer device.

The summary of the data for each iteration of the experiment is shown in Table 1 below:

Table 1: Results of the Cooling Experiment

<td>Iteration</td><td>Description</td><td>T start prom ° c</td><td>Also avg ° c</td><td>Refrigerant T, avg ° C</td><td>fall time of 4 ° C (hh: mm)</td>

<td> 1</td><td>Control case, convection to room only</td><td> 38.8</td><td> 19.6</td><td>N / A</td><td> 02:53</td>

<td> 2</td><td>Driver cooling enabled, Test # 1</td><td> 39.4</td><td> 20.3</td><td> 3.9</td><td> 01:39</td>

<td> 3</td><td>Driver cooling enabled, Test # 2</td><td> 38.1</td><td> 20.4</td><td> 3.5</td><td> 01:38</td>

In Table 1:

T¡n¡c, avg is the initial average temperature of the body to be cooled, the average of two readings

Also avg is the average ambient temperature for the duration of the iteration

Trefrigerante.prom is the average temperature of the refrigerant for the duration of the iteration. Fall time of 4 ° C is the time required to achieve a reduction of 4 ° C in the average temperature of the body to be cooled.

Therefore, conductive cooling through the illustrative heat transfer device used in this Example significantly decreases the time to achieve a 4 ° C reduction in temperature.

Example 2: Operating temperature management

A heat transfer device according to the present technology was used in an animal study as described below. The heat transfer region of the heat transfer device was approximately 70 centimeters in length (to accommodate the length of the muzzle) and had a diameter of approximately 1.4 centimeters, for a surface area of ​​approximately 305 cm²

A large pig with a mass of 70kg was selected to best represent the size and average mass of a human patient. The pig was housed individually in a facility accredited by the International Association for the Evaluation and Accreditation of Laboratory Animal Care (AAALAC), with primary enclosures as specified in the USDA Animal Welfare Act (9 CFR Parts 1, 2 and 3) and described in the Guide for the Care and Use of Laboratory Animals (National Press Academy, Washington DC, 1996).

The pig was anesthetized with a Telozol / Xylazine pre-anesthetic mixture, then given 2% isoflurane inhalation anesthesia after endotracheal intubation was achieved with standard endotracheal intubation equipment and techniques known to those of skill in the art. Muscle paralysis was obtained with

ES 2 575 302 T3 intravenous paralytic. Temperature was continuously monitored by rectal thermocouple probe placed after anesthesia and endotracheal intubation.

A commercially available thermal water bath and circulator (Gaymar Meditherm MTA-5900) was used to provide a temperature controlled heat transfer medium to the heat transfer device. The specific heat transfer medium used was distilled water. The specifications of the commercially available thermal water bath and circulator are as follows:

Dimensions: 94cm H x 35cm W x 48cm D

Weight: 54.9 kg empty; 64.0 kg full

Material: Aluminum Plating, 16 Gauge Steel Frame

Flow Rate: 1 liter per minute

Power: 220V, 240V, 50Hz, 6A

Temperature: Manual: 4 to 42 ° C, Automatic: 30 to 39 ° C

Electric Cable: Detachable 4.6m power cable

The heat transfer device was connected to the circulator and thermal water bath, which was then turned on and allowed to equilibrate while the pig was prepared.

After anesthesia, paralysis, and successful endotracheal intubation of the pig, a central semi-rigid stylet was placed in the heat transfer device and the heat transfer device was lubricated with a biocompatible lubricant.

The heat transfer device was then introduced into the esophagus of the pig using the standard esophageal intubation technique known to those of skill in the art. An external measurement of the distance from the oropharyngeal opening to the xiphoid process served as an indicator of the depth to which the heat transfer device was inserted. Confirmation of adequate insertion depth was obtained by successful aspiration of gastric contents through the gastric lumen of the heat transfer device.

To demonstrate the ability of the heat transfer device to successfully warm a patient under hypothermic conditions typically found in the operating room environment, the pig was cooled by setting the supply temperature of the heat transfer medium to the low set point (4 ° C) for a sufficient time to reduce the temperature of the pig to 33.6 ° C.

Data for the cooling portion of the experiment is shown in Table 2. As can be seen from Table 2, a 1 ° C reduction in core body temperature of a 67.5 kg pig was achieved in approximately 40 minutes; a 2 ° C reduction in core body temperature of a 67.5 kg pig was achieved in approximately 80 minutes; a 3 ° C reduction in core body temperature of a 67.5 kg pig was achieved in approximately 125 minutes; and a 4 ° C reduction in core body temperature of a 67.5 kg pig was achieved in approximately 175 minutes.

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Table 2: Esophageal Cooling

Time (min) Rectal Temperature (° C)

<td> 0</td><td> 37.8</td>

<td> 10</td><td> 37.8</td>

<td> 15</td><td> 37.6</td>

<td> 20</td><td> 37.4</td>

<td> 25</td><td> 37.3</td>

<td> 32</td><td> 37.2</td>

<td> 35</td><td> 37</td>

<td> 40</td><td> 36.8</td>

<td> 45</td><td> 36.7</td>

<td> 50</td><td> 36.6</td>

<td> 55</td><td> 36.4</td>

<td> 60</td><td> 36.3</td>

<td> 65</td><td> 36.1</td>

<td> 70</td><td> 36</td>

<td> 75</td><td> 35.9</td>

<td> 80</td><td> 35.7</td>

<td> 85</td><td> 35.6</td>

<td> 90</td><td> 35.5</td>

<td> 95</td><td> 35.4</td>

<td> 100</td><td> 35.3</td>

<td> 105</td><td> 35.2</td>

<td> 110</td><td> 35.1</td>

<td> 115</td><td> 35</td>

<td> 120</td><td> 34.9</td>

<td> 125</td><td> 34.8</td>

<td> 130</td><td> 34.7</td>

<td> 135</td><td> 34.6</td>

<td> 140</td><td> 34.5</td>

<td> 145</td><td> 34.4</td>

<td> 150</td><td> 34.4</td>

<td> 155</td><td> 34.3</td>

<td>₁T₆to₀bla 2: Chill</td><td>oesophageal nto₃. _4.2</td>

<td> 165</td><td> 34.1</td>

<td> 170</td><td> 33.9</td>

<td> 175</td><td> 33.8</td>

<td> 180</td><td> 33.7</td>

<td> 185</td><td> 33.6</td>

Figure 8 shows a comparison between the cooling rate achieved by a heat transfer device of the present technology compared to the cooling rate shown in US Patent Application Publication 2004/0210281 to Dzeng et al. To make an accurate comparison, and to properly account for the differences in mass between the two experiments, the total amount of heat removed in each case is calculated in standard units of Joules. By using a standard specific heat capacity of water (cp = 4.186 J / g C) to model the specific heat capacity of the animal from

ES 2 575 302 T3 experimentation, the heat extracted at each determined moment is calculated as Q = m (AT) cp, where m is the mass of the experimental animal, and ΔΤ is the difference in temperature obtained at each determined moment.

After one hour, the total heat extracted is 439 kJ in one hour (122 watts) with a heat transfer device of the present technology, compared to a total heat extraction of 260 kJ in one hour (72 watts) achieved with the device mentioned by Dzeng et al. in United States Patent Application Publication 2004/0210281.

The results of the pig cooling experiment show that even in a relatively large animal, with a correspondingly higher heat reserve capacity, a significantly higher heat transfer rate can be achieved with a heat transfer device of the present technology than with prior devices such as those mentioned by Dzeng et al. in United States Patent Application Publication 2004/0210281. From the data presented, the total heat removed, and the consequent cooling achieved, can be seen to be significantly higher with a heat transfer device of the present technology compared to the heat transfer rate and cooling achieved with prior devices such such as those mentioned by Dzeng et al. in United States Patent Application Publication 2004/0210281. Therefore, it was unexpectedly and surprisingly observed that the cooling rate achieved with a heat transfer device of the present technology is significantly higher than that achieved with other devices and that the methods and devices of the present technology transfer more heat. per unit of time than other devices. Without wishing to be bound by any particular theory, it is believed that these unexpected discoveries can be attributed to, for example, one or more of the following characteristics of the heat transfer device: the increased contact surface between the heat transfer region of the device heat transfer and patient anatomy; the reduction in resistance to heat transfer through the device achieved by manufacturing heat transfer devices of the present technology with thinner wall thicknesses; the superior heat transfer characteristics of the materials used to construct the heat transfer devices of the present technology; and the reduction of gastric pressure through gastric ventilation.

After cooling, the reference temperature of the heat transfer medium was changed to a heating mode (42 ° C).

To continue the hypothermia simulation by inducing operating room conditions, the pig was left exposed to room temperature (22 ° C), continuously anesthetized with inhalation anesthesia, paralyzed with a non-depolarizing paralytic to prevent shivering, and with a continuous flow of intravenous hydration of fluids at stable room temperature.

The data from the heating and maintenance phase of the experiment are shown in Table 3. The data in Table 3 demonstrate an initial maintenance of the pig's body temperature at 33.6 ° C, followed by a safe and gradual successful increase. in body temperature for the duration of the experiment. Figure 9 shows the total amount of heat transferred, as calculated above, during the heating and holding phase of the experiment.

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Table 3: Heating and Operating Temperature Management

<td>Time (min)</td><td>Rectal Temperature (° C)</td>

<td> 0</td><td> 33.6</td>

<td> 5</td><td> 33.6</td>

<td> 10</td><td> 33.6</td>

<td> 15</td><td> 33.7</td>

<td> 20</td><td> 33.7</td>

<td> 25</td><td> 33.8</td>

<td> 30</td><td> 33.8</td>

<td> 35</td><td> 33.8</td>

<td> 40</td><td> 33.8</td>

<td> 45</td><td> 33.8</td>

<td> 50</td><td> 33.9</td>

<td> 55</td><td> 33.9</td>

<td> 60</td><td> 33.9</td>

<td> 65</td><td> 33.9</td>

<td> 70</td><td> 33.9</td>

<td> 85</td><td> 34</td>

<td> 100</td><td> 34.1</td>

<td> 115</td><td> 34.2</td>

<td> 130</td><td> 34.3</td>

<td> 145</td><td> 34.3</td>

<td> 160</td><td> 34.3</td>

<td> 175</td><td> 34.4</td>

<td> 190</td><td> 34.5</td>

<td> 205</td><td> 34.5</td>

Consequently, the data demonstrate that a heat transfer device of the present technology can maintain, and increase, body temperature while the patient is exposed to hypothermic conditions adverse to the operating room environment.