Patent Publication Number: US-2015073516-A1

Title: Evaporative Therapeutic Hypothermia Device

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit of U.S. Provisional Patent Application No. 61/621,697 filed on Apr. 9, 2012, which is incorporated by reference, herein, in its entirety. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates generally to neonatal care. More particularly the present invention relates to a device for providing therapeutic hypothermia to a neonate. 
     BACKGROUND OF THE INVENTION 
     Hypoxic ischemic encephalopathy (HIE) is a serious condition that leads to death and disabilities in neonates due to oxygen deficiency in the brain. Asphyxia in neonates can be caused by a variety of factors such as maternal malnutrition, placental abruption, cord prolapse, and uterine rupture. On a global scale, between 50% and 89% of infants who suffer from severe HIE die, while many of the survivors are subject to cerebral or neural related disorders. Additionally, there is 20% to 37% mortality and morbidity in those diagnosed with moderate HIE. Because of the steep differences in HIE severity, HIE has become a major concern worldwide, and the high chances of poor outcome for those suffering from the disease suggest a significant need for improved treatment. This is especially true in developing countries, where the rate of being diagnosed with HIE is as high as 1.5% of newborns. 
     Studies have shown that the use of therapeutic hypothermia not only reduces the risk of death but also the possibility of long-term disability for infants who survive birth asphyxia. By slowing down the formation of free radicals and preventing apoptosis and necrosis in neurons, hypothermia has been proven to be a neuroprotective mechanism against HIE within 6 hours of birth. After 6 hours, however, neuroprotection is seemingly lost, which minimizes the effectiveness of the treatment and could instead result in adverse effects. In addition, the infant must be at least 35 weeks of gestation and weigh more than 1800 grams in order to be considered for therapeutic hypothermia. 
     Therapeutic hypothermia treatments do exist, and are the standards of care in many developed nations. In the United States, the current procedure for therapeutic hypothermia is a whole body cooling in which the infant is placed on a cooling blanket with an esophageal temperature probe inserted into the nose for a total of 72 hours. While on the blanket, the baby is cooled using a temperature between 3° C. and 5° C. Once the baby reaches a core temperature of 34° C., cooling is done in a servo manner to reach the target temperature of 33.5° C. to avoid overcooling. After the target temperature is maintained for a period of 72 hours, an 8 to 10 hour rewarming process begins during which the baby is warmed at a gradual rate of 0.5° C. per hour until it reaches a core temperature of 36.5° C. and stabilizes. 
     Currently, therapeutic hypothermia treatments are not a viable standard of care in developing nations. Existing treatments are too expensive and have an electricity demand that surpasses the availability of power in many countries. Attempts to develop low-cost, low-energy therapeutic hypothermia devices have been unsuccessful. Examples of such attempts include the use of fans in South Africa, which lacked any method of control, and the implementation of cold water bottles around the baby in Uganda, which resulted in overshoot and an increase in side effects (i.e. coagulopathy) and mortality. 
     It would therefore be advantageous to provide a device that provides low-cost, low-power therapeutic hypothermia for use in developing nations. 
     SUMMARY 
     According to a first aspect of the present invention a device for providing therapeutic hypothermia to a neonate includes a first receptacle, having a first wall defining a first inner volume. The device also includes a second receptacle which is configured to sit within the first inner volume of the first receptacle. The second receptacle has a second wall defining a second inner volume, and the second inner volume is configured to receive the neonate. A third inner volume is defined between the first wall of the first receptacle and the second wall of the second receptacle, and a porous material is disposed in the third inner volume. A first sensor is configured to take a temperature of a skin of the neonate, and a second sensor is configured to take a rectal temperature of the neonate. 
     In accordance with an aspect of the present invention, the first receptacle takes the form of a clay pot. The second receptacle can also take the form of a clay pot. However, the second receptacle can also take the form of a basket formed from a natural fiber. The porous material filling the third volume is sand, and in some embodiments can include a cooling material such as ammonium nitrate. The device also includes a water reservoir. A biocompatible liner is disposed in the second receptacle to form a layer of protection between the second receptacle and the neonate. 
     In accordance with another aspect of the present invention, the device can include a visual display of the temperature of the neonate. More particularly, the device can include a temperature control system having a microprocessor receiving information from the first and second sensors. In such a case, a visual display of the temperature, is also included, and the visual display of the temperature is controlled by the microprocessor of the temperature control system. The visual display of the temperature further includes LED lights and/or an auditory alarm alert. An elevation system, such as a block, configured to raise the neonate off of a surface of the second receptacle is also included. Additionally, the device can include a heart rate monitor and a spO 2  monitor. The device can use battery power or generator power. A warming blanket can be included for the neonate. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The accompanying drawings provide visual representations which will be used to more fully describe the representative embodiments disclosed herein and can be used by those skilled in the art to better understand them and their inherent advantages. In these drawings, like reference numerals identify corresponding elements and: 
         FIGS. 1A and 1B  illustrate perspective views of a device to provide therapeutic hypothermia, according to an embodiment of the present invention. 
         FIG. 2  illustrates a schematic diagram of therapeutic hypothermia cooling, according to an embodiment of the present invention. 
         FIG. 3A  illustrates a schematic diagram of a pathway of temperature change, according to an embodiment of the present invention. 
         FIGS. 3B and 3C  illustrate schematic diagrams of the device&#39;s control systems for cooling and warming, according to an embodiment of the present invention. 
         FIG. 4  illustrates a schematic diagram of a control system according to an embodiment of the present invention. 
         FIG. 5  illustrates a schematic diagram representing a method of cooling and warming a neonate using the device of the present invention. 
         FIGS. 6A-6D  illustrates various metrics of temperature in the exemplary embodiment. 
         FIGS. 7A-7C  illustrate results for three piglets in the exemplary embodiment of the present invention. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     The presently disclosed subject matter now will be described more fully hereinafter with reference to the accompanying Drawings, in which some, but not all embodiments of the inventions are shown. Like numbers refer to like elements throughout. The presently disclosed subject matter may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements. Indeed, many modifications and other embodiments of the presently disclosed subject matter set forth herein will come to mind to one skilled in the art to which the presently disclosed subject matter pertains having the benefit of the teachings presented in the foregoing descriptions and the associated Drawings. Therefore, it is to be understood that the presently disclosed subject matter is not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims. 
     The present invention provides a low-cost, low-power therapeutic hypothermia device for use in developing nations. The device includes a first and second receptacle separated by a space filled with a porous material such as sand. A cooling chemical can also be added to the porous material in order to speed cooling. Water is added to the porous material and a neonate is placed into the device for therapeutic hypothermia treatment. The neonate is monitored carefully using temperature sensors and a feedback system integrated into the device. Cooling can be modulated and/or warming commenced by adding Styrofoam blocks to raise the neonate off the surface of the device. 
       FIGS. 1A and 1B  illustrate perspective views of a device to provide therapeutic hypothermia, according to an embodiment of the present invention. As illustrated in  FIGS. 1A and 1B , the device  10  includes a first receptacle  12  and a second receptacle  14 . The first receptacle  12  has a wall  16  defining a first inner volume  18 . The second receptacle  14  is configured to sit within the first inner volume  18  of the first receptacle  12 . The second receptacle  14  also has a wall  20  defining a second inner volume  22 . The second inner volume  22  is configured to receive an infant for therapeutic hypothermia. The first and second receptacles can take the form of clay pots or any other suitable form known to or conceivable by one of skill in the art. Alternately, the first receptacle  12  can take the form of a clay pot and the second receptacle  14  can take the form of a basket lined with plastic or other suitable material. 
     As illustrated in  FIGS. 1A and 1B , a space  26  is also defined between the wall  20  of the second receptacle  14  and the wall  16  of the first receptacle  12 . This space  26  is filled with a porous material  26 , such as sand. A urea-based powder, such as ammonium nitrate can also be added to the sand mixture to further increase heat transfer in the system. While sand and a urea-based powder are provided as examples herein, any suitable porous material and heat transfer enhancement chemical known to one of skill in the art could also be used. 
     The device  10  can also include a polyethylene covering for an inner surface  38  of the wall  20  of the second receptacle  14 . While polyethylene is provided as an example, any biocompatible, covering material known to one of skill in the art could be used. In one exemplary embodiment the second receptacle  14  has approximate dimensions of 16 inches×12 inches×6 inches and the first receptacle  12  has approximate dimensions of 17 inches×13 inches×9 inches. The device  10  can also include a temperature monitoring system  28 , having a microprocessor (not shown), thermistors or temperature sensors  30 , batteries (not shown), such as two AAA batteries, circuit board (not shown), and LED lights  32 . Power can alternately be provided by a generator or other electrical system. The temperature monitoring system  28  can be configured to measure rectal and skin temperature of an infant. The temperature sensors can take the form of temperature probes or skin temperature detectors, or any other sensor known to or conceivable by one of skill in the art. Other sensors can also be included in order to monitor the neonate&#39;s heart rate and spO 2 . 
     As illustrated in  FIG. 1B  the device can also include a water reservoir  34  with a water tube  36  to store and convey water to the porous material between the first and second receptacles  12 ,  14 . The water reservoir  34  and water tube  36  keep the porous material hydrated during the therapeutic hypothermia process. Alternately, the water reservoirs  34  can be integrated into the device  10 , as illustrated in  FIG. 1A , where multiple reservoirs  34  surround the first receptacle  12 . A biocompatible lining  38  is used to protect the baby within the device  10 . 
       FIG. 2  illustrates a schematic diagram of therapeutic hypothermia cooling, according to an embodiment of the present invention. With regard to the present invention, the lowering of the neonate&#39;s core temperature is achieved through the use of evaporative cooling. A porous material  40  such as wet sand is placed between two receptacles  42 ,  44 . As illustrated in  FIG. 2 , when water is added to the sand, the water particles slowly leave the outer receptacle  42  through small pores in the clay. As the water evaporates, heat is drawn from the inner receptacle  44 , resulting in a lower temperature on a surface  46  of the inner receptacle  44 . 
       FIG. 3A  illustrates a schematic diagram of a pathway of temperature change, according to an embodiment of the present invention. A step  50  includes energy usage and a first transfer function  52  converts this energy usage to cooling or warming in step  54 . A second transfer function  56  converts the cooling or warming  54  to a change in skin temperature  58 . A third transfer function  60  converts the change in skin temperature  58  to a change in rectal temperature  62 . A control system  64  monitors this change in rectal temperature to determine how long this loop should be executed in order to reach and maintain the optimal temperature for the particular neonate. Each step is modeled with transfer functions. An inner receptacle surface temperature of 17° C. is sufficient to lower the inner body temperature of the neonate to 33.5° C. Mathematical models indicate that this decrease in the neonate&#39;s temperature takes approximately one and a half hours. 
       FIGS. 3B and 3C  illustrate schematic diagrams of the device&#39;s control systems for cooling and warming, according to an embodiment of the present invention.  FIG. 3B  illustrates a step  70  of monitoring a baby&#39;s temperature and a step  72  of determining whether the temperature meets the reference temperature of 32.5-34.5° C. If no, step  74  includes increasing heating or cooling of the baby, and, if yes, step  76  includes continued monitoring of the baby.  FIG. 3C  illustrates a step  80  of monitoring the baby&#39;s temperature and a step  82  of determining whether the temperature meets a reference rate of 0.5° C./hr. If no, step  84  includes increasing heating or cooling of the baby, and, if yes, step  86  includes continued monitoring of the baby. 
       FIG. 4  illustrates a schematic diagram of a control system according to an embodiment of the present invention. The control system  90  functions primarily through a peripheral interface controllers (PIC) microcontroller from  FIG. 1A  and first and second LED alert lights  94 ,  96 . Preferably, the LED alert lights  94 ,  96  are yellow and green in color, respectively, however, any suitable color indicator can also be used. Alerts can also take the form of sound or other means of alerting a technician that action should be taken. The microcontroller is programmed in conjunction with an individualized circuit containing thermistors  98 ,  100  to provide temperature feedback and to help achieve the specific temperature ranges that the neonate must be kept in during the cooling and warming processes. The first LED alert light  94  indicates that the baby&#39;s core temperature is either falling too low or rising too high, while the second LED alert light  96  indicates that the baby&#39;s core temperature is increasing at a maximum rate of 0.5° C./hr. In addition, there are three supplemental LED lights on the side of the outer pot corresponding to three different heights at which the baby may be elevated or lowered, as illustrated in  FIG. 1B . For example, if the baby is cooled too fast, the top LED light will turn on to indicate that the baby needs to be elevated to the maximum height to reduce cooling. On the other hand, if the baby is being warmed at a rate faster than 0.5° C./hr, then the middle or the lowest LED light will be turned on to alert a nurse to lower the baby for effective treatment to continue. Our control system, which many developing world devices currently lack, is a simple and elegant yet requires minimal input from a health care professional. 
       FIG. 4  further illustrates the diagram of the control system circuit  90 . The microprocessor  28  uses a temperature reading from a rectal monitoring sensor  98  to determine which LED light to turn on. A first LED alert light  94  will be turned on to warn a nurse that the rectal temperature is not within the desired temperature range, while a second LED alert light  96  will be turned on if the rectal temperature is within 33.5±1° C. during cooling. A skin monitoring sensor  100  is used as an additional safeguard to prevent any drastic change in temperature and dangers caused by a failure of rectal monitoring. The skin sensor  100  is placed on a patient&#39;s abdomen to make sure that the neonate&#39;s skin temperature is not too low or too high. The same indicating LEDs  94 ,  96  are used to indicate temperature variability to healthcare providers. 
     After the neonate has been cooled to the predetermined temperature, the neonate must then be warmed. A maximum rate of warming of 0.5° C. is required in order to avoid health risks associated with rapid rewarming Therefore, controlled passive warming is used to reduce the possibility of overshoot in warming. Passive warming allows the rate of temperature increase to occur more gradually, and also reduces the amount of energy required to operate the device. 
     In order to initiate warming, water is no longer added to the sand. This allows passive warming to occur more readily. Passive warming is controlled by raising and lowering the neonate out of and into the device. In order to raise the neonate&#39;s temperature, the neonate is lifted, and a small block, such as a Styrofoam block is placed underneath the baby inside the inner pot. Raising the neonate lifts it from the cool surface of the clay, allowing the neonate to undergo passive warming. Additional blocks can be added inside the inner pot to further increase the warming rate. On the other hand, to slow down the rate of temperature increase or to maintain a stable cool temperature, blocks can be removed to lower the neonate back to the inner pot. Therefore, lowering or raising the neonate from the inner pot using the blocks allows us to utilize the temperature gradient of the inner pot to regulate the neonate&#39;s core body temperature. 
     Passive warming might not be sufficient for warming a neonate. In such a case, an active warming process is required. A simple and cost-effective way to implement an active warming is via Kangaroo Mother Care (KMC). KMC is a World Health Organization promoted technique in which the neonate is held close to the chest of the mother, or an attending nurse to allow excessive heat to transfer from the caretaker to the neonate. Should the neonate receiving therapeutic hypothermia treatment require a large increase in temperature, KMC will be applied to the newborn. 
       FIG. 5  illustrates a schematic diagram representing a method of cooling and warming a neonate using the device of the present invention. A neonate born asphyxiated is identified in step  110 . The neonate is placed into a device according to the present invention as described with respect to  FIGS. 1A and 1B  in step  112  and water is added to the device. Step  114  includes cooling the neonate, while using thermometers to determine whether the neonate&#39;s temperature is too high or too low. Step  116  includes adding a Styrofoam block in order to raise the temperature of the neonate, and step  118  includes adding a second Styrofoam block in order to raise the temperature of the neonate further. After the neonate is cooled to the appropriate temperature, warming can begin. In step  120  the neonate remains on the Styrofoam blocks in the device and is wrapped in a blanket for warming In order to achieve more aggressive warming, KMC can also be used, as illustrated in step  122 , such that the neonate is warmed at a rate of &gt;0.5° C./hr. It should be noted that there is a 6 hour grace period in which to begin cooling the neonate. Cooling should extend for approximately 72 hours, during which time the neonate&#39;s temperature is kept at 33.5°, and warming should be performed for &gt;7 hours. 
     EXAMPLE 
     An exemplary implementation of the present invention is described herein, in order to further illustrate the present invention. The exemplary implementation is included merely as an example and is not meant to be considered limiting. Any implementation of the present invention on any suitable subject known to or conceivable by one of skill in the art could also be used, and is considered within the scope of this application. 
     In order to test the more practical efficacy of the present invention, three piglets (n=3; 2-10 days old; 1800±400 g), were used in a proof of concept experiment. Piglets were used as a model for neonates, because the stage of neuronal development is similar to that of a neonate. Piglets are anesthetized by breathing 5% Isoflurane in a 70/30 nitrous oxide/oxygen mixture by face mask. A tracheotomy is performed, and the lungs are mechanically ventilated with 1.5% Isoflurane in a 70/30 nitrous oxide/oxygen mixture. A rectal temperature probe is placed. Piglets undergo aseptic surgery for placement of sterile catheters into the femoral artery and vein through an incision in the groin. A solution of 5% dextrose and 0.45% saline are infused at a maintenance rate of 4 mL/kg/h. Pharmaceutical grade fentanyl is infused (20 mcg/kg+20 mcg/kg/h, IV). Pharmaceutical grade pancuronium is administered (0.2 mg/kg+0.2 mg/kg/h, IV) to facilitate electrocauterization of the muscle layers and to prevent shivering with hypothermia and rewarming The Isoflurane concentration will be increased, additional fentanyl boluses (20 mcg/kg) will be administered, and the fentanyl infusion will increased for animal comfort if the animal&#39;s heart rate exceeds 200 beats per minute (bpm) without any other apparent cause (such as hypoventilation) or if blood pressure or heart rate increase by 10% or more during surgery. (A normal heart rate for a piglet is approximately 140-200 bpm). 
     Throughout piglet testing, temperature is checked at least every 10 minutes. To set up the device, sand and half a urea-based cooling packet powder are mixed and placed in between the two pots. To initiate cooling, 600 mL of tap water (24-39° C.) are added to the sand and urea-based powder layer, with care taken to avoid spilling water into the inner pot. The piglet is cooled until it reaches 34° C., at which point it should be elevated fully and a blanket is placed on top for passive warming Once every half hour, a heating blanket was placed on the piglet for 10 minutes in order to mimic KMC. It was found that 10 minutes of heating allows the temperature of the piglet to increase at the correct rate. After warming for 10 minutes with the heating blanket, the piglet is placed back in the receptacle. Elevation is changed in order to maintain the new temperature achieved with the heating blanket. Even while the piglet is elevated, an inner pot temperature of 17-19° C. should be maintained. If the pot starts to warm, more water is added. 
     By placing wet sand between two receptacles, adding water to the sand, and measuring room and inner-pot temperatures, the effectiveness of cooling was determined.  FIGS. 6A-6D  illustrates various metrics of temperature in the exemplary embodiment.  FIG. 6B  illustrates that the inner pot surface temperature was able to reach 17° C. within 1 hour, which is the target temperature required to cool down 33.5° C. of a neonate. In addition, the device maintained this temperature without much variability, even with changes in room temperature, for over 24 hours, at which point the experiment was stopped, as illustrated in  FIG. 6D . 
       FIGS. 7A-7C  illustrate results for three piglets in the exemplary embodiment of the present invention. With the first piglet, as illustrated in  FIG. 7A , only the ability to cool piglets was tested. It was found that the first piglet reached the target rectal temperature in 1 hour and 45 minutes, approximately matching the mathematical modeling predictions. However, there was an overshoot in cooling, indicating that passive warming is required to prevent overcooling, as illustrated in  FIG. 7A . 
     The second piglet tested elevation as a passive warming method. The target temperature was reached in about 25 minutes. However, the piglet was also underweight. Temperature stabilized at around 30.4° C. once passive warming had been started, and this temperature was maintained for over 3 hours, as illustrate in  FIG. 7B . 
     During the third piglet test, passive warming was started early to prevent the overshoot seen in previous trials. The piglet reached the target temperature of 33.5° C. around 45 minutes and there was no overshoot in the cooling. Though it was not allowed to test KMC on piglet due to the animal protocol, we calculated the amount of heat flow required to simulate KMC (Supplementary  FIG. 2 ). When the simulation was tested with a heating blanket, it was found that the core temperature is kept constant at the warmer temperature after the application of KMC for 50 minutes. Therefore, the results satisfied the warming constraint of 0.5 c/hr, as illustrated in  FIG. 7C . 
     Although the present invention has been described in connection with preferred embodiments thereof, it will be appreciated by those skilled in the art that additions, deletions, modifications, and substitutions not specifically described may be made without departing from the spirit and scope of the invention as defined in the appended claims.