Methods and devices for non-invasive cerebral and systemic cooling
09775741 · 2017-10-03
Assignee
Inventors
- Denise Barbut (New York, NY)
- Alan Rozenberg (San Diego, CA, US)
- John K Hoffman (Poway, CA, US)
- Thomas H Shaffer (Chadds Ford, PA, US)
Cpc classification
A61M2025/0073
HUMAN NECESSITIES
A61M2025/0034
HUMAN NECESSITIES
A61M25/003
HUMAN NECESSITIES
A61M25/0068
HUMAN NECESSITIES
A61M16/0479
HUMAN NECESSITIES
A61M25/0032
HUMAN NECESSITIES
A61F7/12
HUMAN NECESSITIES
A61M31/00
HUMAN NECESSITIES
A61M25/007
HUMAN NECESSITIES
International classification
A61F7/12
HUMAN NECESSITIES
Abstract
Methods for cerebral cooling are described. Cooling assemblies include elongate tubular members, a reservoir containing a pressurized fluid, and a manifold connecting the reservoir and elongate tubular members. After insertion of the elongate tubular members into the patient's nostrils, a pressurized fluid is delivered onto a surface of the patient's nasal cavity through a plurality of ports in the elongate tubular members. The delivery of the fluid causes cooling by direct heat transfer through the nasopharynx and hematogenous cooling through the carotids and the Circle of Willis.
Claims
1. A method for cerebral cooling, comprising the steps of: providing a cooling assembly comprising: a first elongate tubular member adapted for insertion into a nasal cavity of a patient through a patient's first nostril, the first elongate tubular member comprising a proximal end, a distal end, a lumen extending therebetween, and a plurality of ports in fluid communication with the lumen; a second elongate tubular member adapted for insertion into a nasal cavity of a patient through the patient's second nostril, the second elongate tubular member comprising a proximal end, a distal end, a lumen extending therebetween, and a plurality of ports on the distal end of the second elongate tubular member in communication with the lumen; a manifold in fluid communication with the lumens of the first and second elongate tubular members, the manifold further communicating with a third elongate tubular member; and a reservoir containing a pressurized fluid in communication with the third elongate tubular member, wherein the pressurized fluid has a boiling point less than 37° C.; inserting the first elongate tubular member into a patient's nasal cavity through the patient's first nostril such that the plurality of ports are positioned in the nasal cavity; inserting the second elongate tubular member into the patient's nasal cavity through the patient's second nostril such that the plurality of ports are positioned in the nasal cavity; and delivering the pressurized fluid onto a surface of the patient's nasal cavity by infusing the pressurized fluid from the reservoir through the manifold, into the lumens and through the plurality of ports of the first and second elongate tubular members.
2. The method of claim 1, wherein cooling fluid having a boiling point less that 37° C. is selected from the group consisting of a perfluorocarbon, a hydrofluorocarbon, and a fluorocarbon.
3. A method for cerebral cooling, comprising the steps of: providing a cooling assembly comprising: a first elongate tubular member adapted for insertion into a nasal cavity of a patient through a patient's first nostril, the first elongate tubular member comprising a proximal end, a distal end, a lumen extending therebetween, and a plurality of ports in fluid communication with the lumen; a second elongate tubular member adapted for insertion into a nasal cavity of a patient through the patient's second nostril, the second elongate tubular member comprising a proximal end, a distal end, a lumen extending therebetween, and a plurality of ports on the distal end of the second elongate tubular member in communication with the lumen; a manifold in fluid communication with the lumens of the first and second elongate tubular members, the manifold further communicating with a third and a fourth elongate tubular member; and a reservoir containing gas and a pressurized fluid, the pressurized fluid having a boiling point of less than 37° C. in communication with the third elongate tubular member and the gas in communication with the fourth elongate tubular member; inserting the first elongate tubular member into a patient's nasal cavity through the patient's first nostril such that the plurality of ports are positioned in the nasal cavity; inserting the second elongate tubular member into the patient's nasal cavity through the patient's second nostril such that the plurality of ports are positioned in the nasal cavity; and delivering the gas and pressurized fluid onto a surface of the patient's nasal cavity by infusing the gas and pressurized fluid from the reservoir through the manifold, into the lumens and through the plurality of ports of the first and second elongate tubular members.
4. The method of claim 3, wherein the pressurized fluid and gas are delivered onto the surface of the patient's nasal cavity as a nebulized spray.
5. The method of claim 3, wherein the pressurized fluid is a perflurocarbon.
6. The method of claim 5, wherein the perfluorocarbon is selected from the group consisting of perfluorohexane, perfluoropentane, and 2-methyl-perfluoropentane.
7. The method of claim 3, wherein the gas is air, oxygen, or a combination thereof.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
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DETAILED DESCRIPTION
(62) Evaporative Cooling in the Nasal Cavity
(63)
(64) As shown in
(65)
(66) In another alternative embodiment, depicted in
(67) The liquids used with this catheter include liquids having a boiling point of about 38-300° C., more preferably a boiling point of about 38-200° C., more preferably a boiling point of about 60-150° C., more preferably a boiling point of about 70-125° C., more preferably a boiling point of about 75-110° C., more preferably a boiling point of about 60-70° C. Compounds having suitable characteristics for use herein include hydrocarbons, fluorocarbons, perfluorocarbons, and perfluorohydrocarbons. Saline is another example of a substance having suitable characteristics for use herein. As used in this specification, the terms “fluorocarbon,” “perfluorocarbon,” and “perfluorohydrocarbon” are synonymous. In addition to containing carbon and fluorine, these compounds may also contain other atoms. In one embodiment, the compounds could contain a heteroatom, such as nitrogen, oxygen, sulfur, or a halogen, such as bromine or chlorine. These compounds may be linear, branched, or cyclic, saturated or unsaturated, or any combination thereof. Exemplary perfluorocarbons include perfluoropropane, perfluorobutane, perfluoropentane, 2-methyl-perfluoropentane, perfluorohexane, perfluoroheptane, and perfluorooctane.
(68) The liquids delivered through the catheter (single or multi-lumen) may also comprise a humidifier. Alternatively, the humidifier may be delivered separately through the catheter or using an alternative delivery device. When used in conjunction with the cooling liquid, the humidifier would have to be cooled or else it would counteract the cooling effect of the other liquid. Where the humidifier was used independently for humidification, it could also be warmed. The humidifiers may be delivered through the same ports in the catheter as the cooling liquid. Alternatively, a different lumen and/or port in the catheter may be used to deliver the humidifier. The purpose of the humidification is to prevent the sensation of dryness, the crusting and trauma that could result from the dryness, the nasal congestion and mucous production that could result from dryness imparted by the high gas flow rates or from the evaporation of the liquid (e.g., PFC). The congestion and mucous production reduce the effectiveness of the cooling by limiting the cavity in which the evaporation occurs and by directly blocking holes in the catheter. This phenomenon may account for rapid initial cooling rates observed, followed by slower cooling rates beyond the first 20 to 30 minutes.
(69) The humidifier may be, but is not limited to isotonic saline, or water. Where water is used as the humidifier, the quantity needed to be added for full saturation is about 41 micrograms/L of gas. Alternative nasal inhalers, such as but not limited to, ephedrine, pseudoephedrine (e.g., Afrin), antihistamines, ipratropium (e.g., Atrovent), and anticholinergics, may also be used to saturate the air in the nasal cavity.
(70) The gases used with the catheter include any gas capable of evaporating the liquid. The gas can include, but is not limited to, nitrogen, air, oxygen, argon, or mixtures thereof.
(71) In use, as seen in
(72) In addition, the ability to nebulize the liquid at each delivery port ensures that the distribution of varying sizes of liquid particles will be uniform throughout the nasal cavity. Specifically, when a liquid is nebulized, a spray with liquid particles of various sizes is created. If the liquid was nebulized at the proximal end of the nasal catheter or outside of the catheter and then transported as a nebulized liquid spray through the catheter lumen to the multiple delivery ports, the smaller liquid particles would flow through the proximal delivery ports while the larger liquid particles would be carried to the distal end of the tube before being delivered to the nasal cavity via one of the delivery ports near the distal end of the nasal catheter. This would result in an uneven distribution of the liquid particles within the nasal cavity. Conversely, when the liquid is transported through the nasal catheter and nebulized separately at each delivery port just prior to delivery, the size distribution of liquid particles distributed at any given point in the nasal cavity is uniform. This is critical because an even distribution of the varying sized liquid particles provides for better evaporation of the liquid spray, which results in better cooling through evaporative heat loss and is more tolerable to the patient. Furthermore, since the liquid begins to evaporate immediately upon contact with the gas, mixing at the point of use in the patient will ensure efficient use of all available cooling.
(73) The liquid flow rate is also a critical factor for cerebral cooling.
(74) In addition to the liquid flow rate, it has also been shown that the ratio of gas flow rate to liquid flow rate is a critical factor affecting the cerebral cooling within the nasal cavity. Initially, it was thought that increasing the liquid flow rate would increase cooling. The cooling rate, however, only increases if the gas flow is concurrently increased to evaporate the nebulized liquid. This is necessary because the cooling within the nasal cavity is achieved through evaporative heat loss as nebulized liquid evaporates. If the nasal cavity becomes saturated with the evaporated liquid, however, then the evaporation rate decreases and consequently, the cooling rate decreases. Thus, the rate of evaporation is dependent on the concentration of the liquid within the nasal cavity as well as the flow rate of the liquid. Therefore, increasing the liquid flow rate to the nasal cavity only increases the cooling rate if the gas flow rate is also increased to evaporate off the nebulized liquid. The ratio for the liquid delivery rate: gas delivery rate to optimize the evaporation and maintain a constant rate of evaporation preferably ranges from 1:25 mL-1:5000 mL, more preferably from 1:500 mL-1:2000 mL, more preferably from 1:700 mL-1:1500 mL.
(75) The flow rate of the gas and liquid can be altered during the process according changes in a physiological parameter such as the amount of cooling achieved or changes in cerebral blood flow. Feedback can be provided in the form of nose temperature, body temperature, tympanic temperature, brain temperature, rectal temperature, etc. For example, an alarm could be triggered when the body temperature falls below 35° C. and delivery of the fluids and gas could be stopped. Additionally, feedback in the form of the brain temperature or tympanic temperature could be provided such that the rate of delivery of the fluids and gases increases if the cooling rate of the brain is less than about 5° C. in one hour, alternatively less than about 4° C. in one hour, alternatively less than about 3° C. in one hour, alternatively less than about 2° C. in one hour, alternatively less than about 1° C. in one hour. The brain temperature can be measured externally, internally, ultrasonically, by infrared or other waveform. In the alternative, feedback in the form of changes in cerebral blood flow (CBF) or a surrogate for CBF such as brain oxygenation, MR perfusion, transcranial doppler (TCD) flow rates, could be provided such that the rate of delivery of the fluids and gases can be adjusted in response to the changes in cerebral blood flow.
(76) Cooling Calculations
(77) The following calculations estimate the maximum cooling that can be obtained using a unit dose of 2 liters of perfluorohexane. The cooling effect of PFH is related to two aspects of thermodynamics: (1) heat capacity of the liquid, as it is warmed from its temperature at application to that of the body and (2) heat of vaporization as it changes from the liquid to the gas state. The relevant properties of perfluorohexane are as follows: ρ. Density: 1.68 grams/ml c. Specific Heat: 1.09 kJ/kg° C.=0.26 cal/g° C. h. Latent Heat: 85.5 kJ/kg=20.4 cal/g
(78) The calculation for heat transfer due to warming the liquid is:
Q=c*m*(T2−T1) or Q=cmΔT Equation 1:
(79) Where m=the mass of the liquid administered T1 is the temperature of the liquid at administration T2 is the temperature to which the liquid is warmed
(80) In the patient case, the heat removed is calculated using the following assumptions: (1) a unit dose quantity of 2 liters is used; (2) the PFC is administered at 0° C.; and (3) the PFC is warmed completely to body temperature of 37° C.
Q=2000 ml*1.68 g/ml*0.26 cal/g ° C.*(37° C.−0° C.)=32,300 calories
(81) The calculation for heat transfer due to evaporation of the liquid is:
Q=h*m Equation 2:
Therefore, assuming a dose of 2 liters,
Q=2000 ml*1.68 g/ml*20.5 cal/g=68,900 calories
(82) For a 2 liter quantity of liquid, the maximum heat removal=100,000 calories or 100 Kcal. The amount of cooling to the body can be calculated using the following assumptions: (1) patient weight of 70 Kg, (2) specific heat of patient=0.83 cal/g° C., (3) heat generated by metabolism or other sources is negligible, and (4) other heat added or removed from the patient is negligible. After rearranging Equation 1 (ΔT=Q/(c*m)), the net change in temperature of the whole body of the patient can be calculated as follows:
ΔT=100 kcal/(0.83 cal/g° C.*70 kg)=1.72° C.
Therefore, the maximum whole body cooling that could occur from a 2 liter dose is approximately 1.7° C. This should result in a body temperature no lower than 35° C., which should not cause any cold related complications.
(83) The sensitivity, i.e., the resultant temperature change experienced by the patient, will depend on the size of the patient. For a very small patient of 40 Kg (88 pounds), the resultant temperature change is ΔT=100 kcal/(0.83 cal/g°c.*40 kg)=2.1° C. For a very large patient of 100 Kg, the resultant temperature change is ΔT=100 kcal/(0.83 cal/g°c.*100 kg)=0.83° C.
(84) By applying the cooling spray to the nasal cavity, there will be more cooling in the head than the remainder of the body. Calculations can be done to determine how cold the head might become if all the cooling is focused solely in the head. The amount of cooling to the head can be calculated using the following assumptions: (1) mass of head=5 kg, (2) specific heat of head=0.83 (same as rest of body), and (3) heat transfer from body (warming from cerebral blood flow) is negligible.
ΔT=q/(s*m)=100 kcal/(0.83 cal/g° C.*5 kg)=24 Degrees C.
This corresponds to a potential minimum head temperature of 13° C.
(85) The above calculations assume that every bit of the liquid is warmed fully to body temperature and evaporates completely. It is likely that in a clinical setting, there will be incomplete warming and evaporation. Specifically, some of the gas and vapor leaving the body will not be at 37° C., and some of the liquid will trickle out of the patient without contributing to heat transfer. These effects will tend to reduce the cooling from the calculated values.
(86) The head cooling calculation assumes that absolutely no heat will be added to the head from the body. This is, however, a poor assumption. The cerebral blood flow is on the order of 1 L per minute, and assuming that this blood is cooled by only 2 degrees while in the head, the calculation becomes as follows:
Net heat removal=100 Kcal−1000 ml/min*30 min*0.83 cal/g° C.*2° C.=50 Kcal
Therefore, the cooling in the head is reduced by at least half of the previously calculated value to 12° C., for a minimum possible 25° C. head temperature
Experimental Data
(87) In use, the nasal catheter of the present invention was inserted through the nose into the nasal cavity. Temperature was measured at baseline (3 times over 10 minutes) and at every minute or continuously at the ventricle or epidural space, where available, and bladder or rectum during the procedure. A suction catheter was positioned in the patient's mouth to prevent pharyngeal liquid from entering the esophagus and a nasogastric (NG) tube was placed in the patient's stomach to suction any liquid PFC or PFC vapor. NG suction was continuous. Nasal cooling was administered via a nasal catheter with one oxygen/PFC mixer and fan spray nozzle per naris. Nasal prongs were positioned in the narices and secured to the nose by tape. After measurement of baseline temperatures, cooling was initiated. Temperature was monitored until it returned to the baseline value. A portion of the PFC was recovered from the oral suction catheter placed in the back of the patient's throat. This recovered PFC can be reused and recycled. The following parameters were used for the human studies.
(88) Oxygen was delivered at about 20 L/min throughout the delivery period, alternatively at about 30 L/min throughout the delivery period, alternatively at about 40 L/min throughout the delivery period, depending on the patient.
(89) The PFC (e.g., perfluorohexane) was delivered at a rate of about 15 mL/min, alternatively at about 25 mL/min, alternatively at about 35 mL/min, alternatively at about 45 mL/min, alternatively at about 50 mL/min, alternatively at about 55 mL/min, alternatively at about 65 mL/min, alternatively at about 75 mL/min, alternatively at about 80 mL/min, alternatively at about 85 mL/min, alternatively at about 95 mL/min, alternatively at about 100 mL/min, depending on the patient. The liquid flow rate was sometimes started at a lower flow rate (e.g., about 15 mL/min or about 25 mL/min) and increased to a faster flow rate (e.g., about 45 mL/min, about 50 mL/min, or about 100 mL/min). Alternatively, the liquid flow rate was started at a faster flow rate (e.g., about 50 mL/min) and gradually reduced to a slower flow rate (e.g., about 25 mL/min). A total of amount of about 1.0 L of PFC was delivered, alternatively about 1.5 L, alternatively about 2.0 L, depending on the patient.
(90) The delivery period was approximately 20 minutes, alternatively approximately 25 minutes, alternatively approximately 30 minutes, alternatively approximately 35 minutes, alternatively approximately 40 minutes, alternatively approximately 45 minutes.
(91) In one method, oxygen is delivered at about 40 Um/in and PFC is delivered at about 80 mL/min throughout the delivery period. A total of about 2 L of PFC is delivered. The delivery period is approximately 20 to 25 minutes.
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(93) The catheter of the present invention can also be used in combination with other cooling or heating devices. For example, the catheter may be used in combination with a helmet or cooling cap for synergistic cooling as seen in, for example, U.S. Pat. No. 6,962,600, which is hereby expressly incorporated by reference in its entirety. As seen in
(94) In another alternative embodiment, a mask can be used in conjunction with the catheter (single or multi-lumen) to increase the amount of air/oxygen/gas delivered to the nasal cavity. This would result in an increase in the rate of liquid evaporation, and therefore the rate of cooling, without increasing the intranasal pressure. As see in
(95) The catheters of the present invention can also be used as drug delivery catheters for delivery of nebulized drugs to the nasal cavity. It is further contemplated that these drugs may be delivered unaccompanied or may be delivered in addition to a cooling agent to facilitate cerebral cooling. As discussed previously, the ability to nebulize the liquid at each delivery port ensures that the distribution of varying sizes of liquid particles will be uniform throughout the nasal cavity, which provides for better evaporation of the liquid spray. The drug delivery catheter may include, but is not limited to, at least 20 delivery ports, alternatively at least 30 delivery ports, alternatively at least 40 delivery ports, alternatively at least 50 delivery ports, alternatively at least 60 delivery ports. Use of such a drug delivery catheter with nebulizing delivery ports may provide more accurate dosing than existing nasal delivery systems, which suffer from problems of liquid dripping down the patient's throat.
(96) The drug could be provided in a liquid suspension or a mixture. The liquid suspension could utilize various liquid carriers, depending on the drug. Liquid carriers include, but are not limited to, water, saline, PFC, and combinations thereof. Use of saline as a carrier has an advantage in that may drugs are already sold with saline as the carrier. Additionally, there are no suspension problems. Use of a PFC as a carrier has an advantage in that, because the PFC would evaporate, the drug would not be diluted.
(97) Drugs that may be delivered using an intranasal delivery catheter include, but are not limited to, neuroprotective agents and malignant hyperthermia, insulin, β-blockers, β-agonists, antihistamines, contraceptives, anesthetics, painkillers, antibiotics, steroids, aspirin, sumatriptan, Viagra, nitroglycerin, hormones, neurodrugs, anti-convulsants, prozac, anti-epileptics, analgesics, NMDA antagonists, narcan, noxone, naltrexone, anxiolytics, and muscle relaxants.
(98) Other Nasal Catheter Designs
(99) In an alternative embodiment, as seen in
(100) In addition, as seen in
(101) The advantages of this invention include: relative ease of placement; available port provides same function as nasogastric tube; similarity to standard nasogastric tubes in design and use; ease of breathing, speaking, etc., through mouth for the patient; liquid flow rate is not dependent on ventilation and can be set by clinician; high turnover flow through cooling enabled; utilization of well perfused anatomical features; perfluorocarbon is well tolerated in lungs; perfluorocarbon in the stomach is also tolerated, and can be easily suctioned with the gastric portion of the catheter.
(102) The compositions of the invention include liquids having a boiling point of about 38-300° C., more preferably a boiling point of about 38-200° C., more preferably a boiling point of about 60-150° C., more preferably a boiling point of about 70-125° C., more preferably a boiling point of about 75-110° C., more preferably a boiling point of about 60-70° C. Compounds having suitable characteristics for use herein include hydrocarbons, fluorocarbons, perfluorocarbons, and perfluorohydrocarbons. Saline is another example of a substance having suitable characteristics for use herein. As used in this specification, the terms “fluorocarbon,” “perfluorocarbon,” and “perfluorohydrocarbon” are synonymous. In addition to containing carbon and fluorine, these compounds may also contain other atoms. In one embodiment, the compounds could contain a heteroatom, such as nitrogen, oxygen, or sulfur, or a halogen, such as bromine or chlorine. These compounds may be linear, branched, or cyclic, saturated or unsaturated, or any combination thereof.
(103) In another embodiment, the compounds are highly fluorinated compounds, which are compounds containing at least three fluorine atoms. These highly fluorinated compounds may also contain other atoms besides carbon and fluorine. These other atoms include, but are not limited to, hydrogen; heteroatoms such as oxygen, nitrogen, and sulfur; and halogens such as bromine or chlorine. In one embodiment, the number of the atoms that are not carbon or fluorine comprise a minority of the total number of atoms in the compound. These highly fluorinated compounds may be linear, branched, or cyclic, saturated or unsaturated, or any combination thereof. Examples of these compounds include, but are not limited to, C.sub.4F.sub.9Br (b.p. 43° C.), CF.sub.3CF(CF.sub.3)CF═CF.sub.2 (b.p. 51° C.), and CF.sub.3CF(CF.sub.3)CH═CH.sub.2.
(104) In another embodiment, the compounds are hydrofluorocarbons, which are compounds where the number of hydrogen atoms exceeds the number of fluorine atoms. These hydrofluorocarbons may also contain other atoms besides hydrogen, carbon, and fluorine. These other atoms include, but are not limited to, heteroatoms such as oxygen, nitrogen, and sulfur and halogens such as chlorine and bromine. For example, hydrofluorocarbons include, but are not limited to, hydrochlorofluorocarbons, more specifically, hydrochlorofluoralkanes. In one embodiment, the number of the atoms other than carbon and fluorine comprise a minority of the total number of atoms in the compound. These hydrofluorocarbons may be linear, branched, or cyclic, saturated or unsaturated, or any combination thereof.
(105) A mixture of two or more highly fluorinated compounds, hydrofluorocarbons, light fluorocarbons, hydrocarbons, fluorocarbons, perfluorocarbons, perfluorohydrocarbons, or any of the above-mentioned compounds may also be used. The mixture may contain any of the previously mentioned compounds in different phases (e.g., one gas, one liquid). The mixture has a boiling point above 37° C., even though any individual component of the mixture may have a boiling point below 37° C.
(106) Light fluorocarbons are fluorocarbons that have a boiling point below 37° C. These light fluorocarbons may also contain other atoms besides carbon, and fluorine. These other atoms include, but are not limited to, hydrogen; heteroatoms such as oxygen, nitrogen, and sulfur; and halogens such as chlorine and bromine. For example, light fluorocarbons include, but are not limited to perfluorobutane and perfluoropentane. In one embodiment, the number of the atoms other than carbon and fluorine comprise a minority of the total number of atoms in the compound. These light fluorocarbons may be linear, branched, or cyclic, saturated or unsaturated, or any combination thereof.
(107) In certain methods, a liquid having a boiling point of 38-300° C., more preferably having a boiling point of 38-200° C., more preferably having a boiling point of 38-150° C., is selected. The liquid is nebulized to form a mist. The droplets preferably range in size from 0.1-100 microns, more preferably 1-5 microns, more preferably 2-4 microns. The mist is optionally cooled below body temperature and delivered to the airway of a patient so that the patient inhales the mist. Inhalation of the mist causes systemic cooling by heat transfer from the lungs to the cooler mist and/or by evaporative heat loss as the mist evaporates. The administration of the liquid is continued until the systemic temperature is reduced to 35° C. or below, more preferably to 34° C. or below, more preferably to 33° C. or below. The rate of cooling can be adjusted by varying the temperature of the inhalate, the concentration of the responsible compound or compound mixture, the rate of delivery, the particle size, and the percentage of each compound in the mixture.
(108) Nitric oxide or adrenergic agents, such as adrenaline (epinephrine) or albuterol, may be added in minute doses to the compositions described in any of the previously described embodiments. The NO or other agent is inhaled and acts as a potent nasal vasodilator, which improves the rate of action of the cooling mist and counteracts nasal vasoconstriction caused by administering cold substances to the nasal cavity. The NO may be included in an amount of about 2 to about 80 parts per million, in other cases in an amount of about 3 to about 20 parts per million, in other cases in an amount of about 4 to about 10 parts per million, in other cases in an amount of about 5 to about 8 parts per million, in other cases in an amount of about 5 parts per million.
(109) In other methods, administration of cold mists will occur in cycles with intervening cycles of administering another gas, preferably a cold dry gas such as dry air or dry heliox, e.g., a mixture of helium and oxygen. With continuous administration of perfluorocarbon mist, the gaseous phase in the nasal cavity may become saturated with gaseous PFC, thereby slowing the rate of evaporative heat loss. In order to accelerate the rate of evaporative heat loss, it may be desired to periodically purge nasal cavity of perfluorocarbon. This can be done by cycling administration of cold mists with administering another gas, preferably a dry gas such as dry air or dry heliox.
(110) Where cycling is desired, it is recommended that the cycles occur for about 3 seconds or more, in other cases for about 30 seconds or more, in other cases for about one minute or more, in other cases for about two minutes or more, in other cases for about five minutes or more, in other cases for about ten minutes or more, in other cases for about 30 minutes or more. The intervening cycle of dry gas may last for an equal period (e.g., about 3 seconds of cold mist followed by about 3 seconds of dry gas, about 30 seconds of cold mist followed by about 30 seconds of dry gas, about one minute of cold mist followed by about one minute of dry gas, about two minutes of cold mist followed by about two minutes of dry gas, about five minutes of cold mist followed by about five minutes of dry gas, about ten minutes of cold mist followed by about ten minutes of dry gas, about 30 minutes of cold mist followed by about 30 minutes of dry gas, or for a shorter or longer period (about ten minutes of cold mist followed by about two minutes of dry gas).
(111) In certain methods, a liquid having a boiling point of 38-300° C. is selected. The liquid is nebulized to form a mist. The droplets preferably range in size from 1-5 microns. The mist is delivered to the nasal and or oral cavities of a patient so that the mist causes cerebral cooling by heat transfer to the cooler mist and/or by evaporative heat loss. In addition indirect hematogenous cooling occurs through the carotids as they pass by the oropharynx and through the Circle of Willis which lies millimeters away from the pharynx. The administration of the liquid is continued until the cerebral temperature is reduced to 35° C. or below, more preferably to 34° C. or below, more preferably to 33° C. or below. In certain methods, the administration of the liquid may be continued to provide for systemic cooling as well as cerebral cooling. In certain methods, the liquid may be cooled to below body temperature before delivery. The mist droplets may range in size from 1-5 microns.
(112) The table in
(113)
(114) TABLE-US-00001 TABLE 1 TIME 1:HEAD-F 1:HEAD-V HEAD-S 1:ESOPH 1:IM 1:SUBQ 1:RECTAL 12:26:52 37.7 38.1 38.5 36.8 38.5 36.7 38.4 12:26:56 37.7 38.1 38.5 36.7 38.5 36.7 38.4 12:27:01 37.7 38.1 38.5 36.5 38.4 36.7 38.4 12:27:05 37.7 38.1 38.5 35.8 38.4 36.7 38.4 12:27:09 37.7 38.1 38.5 35.2 38.4 36.7 38.3 12:27:13 37.6 38.1 38.5 35 38.4 36.7 38.4 12:27:17 37.6 38 38.4 34.6 38.4 36.7 38.3 12:27:21 37.6 37.9 38.4 34.2 38.4 36.7 38.3 12:27:26 37.5 37.8 38.4 34 38.4 36.7 38.4 12:27:30 37.4 37.8 38.5 33.3 38.5 36.7 38.4 12:27:34 37.3 37.7 38.5 33.1 38.4 36.7 38.3 12:27:38 37.3 37.7 38.4 32.9 38.4 36.7 38.3 12:27:42 37.2 37.6 38.4 32.8 38.3 36.7 38.3 12:27:46 37.1 37.6 38.4 32.5 38.3 36.7 38.3 12:27:50 37.1 37.5 38.3 32.5 38.4 36.7 38.4 12:27:55 37 37.5 38.3 32.3 38.4 36.7 38.3 12:27:59 36.9 37.4 38.3 32.2 38.4 36.7 38.3 12:28:03 36.9 37.4 38.3 32.2 38.4 36.7 38.3 12:28:07 36.8 37.4 38.3 32.2 38.5 36.7 38.3 12:28:11 36.7 37.3 38.3 32.1 38.4 36.7 38.4 12:28:15 36.7 37.3 38.3 31.8 38.4 36.7 38.3 12:28:20 36.7 37.3 38.3 31.7 38.4 36.7 38.4 12:28:24 36.6 37.2 38.3 31.6 38.4 36.8 38.4 12:28:28 36.4 37.2 38.2 31.5 38.4 36.7 38.4 12:28:32 36.5 37.2 38.3 31.3 38.5 36.7 38.3 12:28:36 36.5 37.1 38.2 31.2 38.4 36.7 38.4 12:28:40 36.5 37.1 38.2 31.1 38.4 36.7 38.3 12:28:44 36.4 37.1 38.2 31.1 38.4 36.8 38.4 12:28:49 36.3 37.1 38.2 31 38.4 36.7 38.3 12:28:53 36.3 37 38.1 30.9 38.4 36.7 38.3 12:28:57 36.2 37 38.1 30.9 38.4 36.7 38.4 12:29:01 36.2 37 38.1 30.8 38.4 36.7 38.3 12:29:05 36.2 37 38.1 30.7 38.4 36.7 38.3 12:29:09 36.1 36.9 38.1 29.9 38.4 36.7 38.3 12:29:13 36.1 36.9 38.1 29.8 38.4 36.7 38.3 12:29:18 36.1 37 38.1 30 38.4 36.7 38.3 12:29:22 36 37 38.1 30.1 38.4 36.7 38.3 12:29:26 36.1 37 38.1 30.5 38.4 36.7 38.3 12:29:30 36 37 38 30.5 38.4 36.7 38.3 12:29:34 36 37 38 30.6 38.5 36.7 38.3 12:29:38 36 36.9 38 30.6 38.4 36.7 38.3 12:29:43 36 36.9 38 30.6 38.4 36.7 38.3 12:29:47 35.9 36.8 38 30.2 38.4 36.7 38.3 12:29:51 35.9 36.8 38 30.3 38.4 36.7 38.3 12:29:55 35.9 36.8 38 30.2 38.4 36.7 38.3 12:29:59 35.8 36.8 37.9 30.3 38.4 36.7 38.3 12:30:03 35.8 36.8 38 30.3 38.4 36.7 38.3 12:30:07 35.8 36.7 37.9 30.5 38.4 36.7 38.3 12:30:12 35.7 36.7 37.8 30.5 38.4 36.7 38.3 12:30:16 35.7 36.7 37.9 30.6 38.5 36.7 38.3 12:30:20 35.7 36.7 37.8 30.6 38.4 36.7 38.3 12:30:24 35.7 36.6 37.8 30.6 38.4 36.7 38.3 12:30:28 35.6 36.6 37.8 30.5 38.4 36.7 38.3 12:30:32 35.6 36.6 37.8 30.2 38.4 36.7 38.3 2:30:36 35.6 36.6 37.8 30.5 38.4 36.7 38.3 12:30:41 35.6 36.6 37.7 30.5 38.4 36.7 38.3 12:30:45 35.5 36.5 37.7 30.3 38.4 36.7 38.2 12:30:49 35.5 36.5 37.7 30.2 38.4 36.7 38.3 12:30:53 35.5 36.5 37.7 30.2 38.4 36.7 38.3 12:30:57 35.5 36.5 37.7 30.1 38.4 36.7 38.2 12:31:01 35.3 36.4 37.6 30.2 38.3 36.6 38.2 12:31:06 35.3 36.4 37.6 30.1 38.4 36.7 38.2 12:31:10 35.3 36.5 37.6 30.1 38.4 36.7 38.2 12:31:14 35.3 36.5 37.6 30 38.4 36.6 38.2 12:31:18 35.3 36.5 37.6 30.1 38.4 36.7 38.3 12:31:22 35.2 36.4 37.6 30.2 38.4 36.7 38.2 12:31:26 35.2 36.4 37.6 30.2 38.4 36.7 38.2 12:31:30 35.2 36.3 37.6 30.2 38.4 36.7 38.2 12:31:35 35.1 36.3 37.5 30.1 38.4 36.6 38.2 12:31:39 35.1 36.3 37.5 30.1 38.3 36.6 38.2 12:31:43 35.1 36.3 37.5 30.2 38.4 36.7 38.2 12:31:47 35.1 36.3 37.5 30.1 38.4 36.6 38.2 12:31:51 35.1 36.3 37.5 30.1 38.3 36.7 38.2 12:31:55 35.1 36.3 37.4 30.2 38.4 36.6 38.2 12:31:59 35.1 36.3 37.5 30.2 38.3 36.6 38.2 12:32:04 35 36.2 37.4 30.1 38.4 36.6 38.2 12:32:08 35 36.2 37.4 30.1 38.4 36.6 38.2 12:32:12 35 36.2 37.4 30.1 38.4 36.6 38.2 12:32:16 34.9 36.2 37.4 30.1 38.4 36.6 38.2 12:32:20 34.9 36.2 37.4 30.1 38.4 36.6 38.2 12:32:24 34.9 36.1 37.3 30.1 38.4 36.6 38.2 12:32:29 34.8 36.1 37.3 30.1 38.4 36.6 38.2 12:32:33 34.8 36.1 37.3 30 38.4 36.7 38.2 12:32:37 34.8 36.1 37.3 30 38.3 36.6 38.1 12:32:41 34.8 36.1 37.2 29.8 38.3 36.6 38.1 12:32:45 34.8 36.1 37.2 29.8 38.3 36.6 38.2 12:32:49 34.8 36 37.2 29.8 38.4 36.6 38.2 12:32:53 34.7 36 37.2 29.8 38.4 36.6 38.2 12:32:58 34.7 36 37.2 29.8 38.3 36.6 38.2 12:33:02 34.7 36 37.1 29.8 38.3 36.6 38.1 12:33:06 34.7 36 37.1 29.5 38.3 36.6 38.1 12:33:10 34.7 36 37.1 29.5 38.3 36.6 38.1 12:33:14 34.7 36 37.1 29.5 38.3 36.6 38.2 12:33:18 34.6 35.9 37.1 29.5 38.3 36.6 38.1 12:33:23 34.6 36 37.1 29.5 38.4 36.6 38.1 12:33:27 34.6 36 37.1 29.5 38.4 36.6 38.1 12:33:31 34.6 35.9 37.1 29.5 38.3 36.6 38.1 12:33:35 34.6 35.9 37.1 29.4 38.3 36.6 38.1 12:33:39 34.6 35.9 37 29.3 38.3 36.6 38.1 12:33:43 34.6 36 37 29.4 38.4 36.6 38.1 12:33:47 34.6 36 37 29.3 38.3 36.6 38.1 12:33:52 34.6 36 37 29.3 38.3 36.6 38.1 12:33:56 34.6 36 37 29.2 38.3 36.6 38.1 12:34:00 34.7 36 37 29.2 38.3 36.6 38.1 12:34:04 34.7 36 37 29.2 38.4 36.7 38.2 12:34:08 34.6 36 37 29.1 38.3 36.6 38.1 12:34:12 34.6 36 37 29.2 38.3 36.6 38.1 12:34:16 34.6 36 37 29.1 38.3 36.6 38.1 12:34:21 34.6 36 36.9 29.1 38.3 36.6 38.1 12:34:25 34.6 36 36.9 29 38.3 36.6 38.1 12:34:29 34.6 35.9 37 29 38.4 36.6 38.1 12:34:33 34.5 35.9 36.9 29 38.3 36.6 38.1 12:34:37 34.5 35.9 36.9 28.9 38.3 36.6 38.1 12:34:41 34.5 35.9 36.9 28.9 38.3 36.6 38.1 12:34:46 34.5 35.9 36.9 28.9 38.3 36.6 38.1 12:34:50 34.5 35.8 36.8 28.8 38.3 36.6 38.1 12:34:54 34.5 35.8 36.8 28.8 38.3 36.6 38.1 12:34:58 34.5 35.8 36.8 29 38.3 36.6 38.1 12:35:02 34.4 35.8 36.8 29.1 38.3 36.6 38.1 12:35:06 34.5 35.8 36.8 29.1 38.3 36.6 38.1 12:35:11 34.4 35.7 36.8 29 38.3 36.5 38.1 12:35:15 34.3 35.7 36.8 29 38.3 36.6 38 12:35:19 34.3 35.7 36.8 29 38.3 36.6 38.1 12:35:23 34.2 35.6 36.7 28.9 38.3 36.6 38 12:35:27 34.2 35.6 36.7 29 38.3 36.5 38 12:35:31 34.2 35.6 36.7 29.1 38.3 36.5 38 12:35:35 34.2 35.7 36.7 29.1 38.3 36.5 38 12:35:40 34.2 35.7 36.7 29.1 38.3 36.5 38.1 12:35:44 34.2 35.7 36.7 29.2 38.3 36.5 38 12:35:48 34.2 35.6 36.7 29.2 38.3 36.5 38 12:35:52 34.2 35.6 36.6 29.2 38.3 36.5 38 12:35:56 34.1 35.5 36.6 29.2 38.3 36.5 38 12:36:00 34.1 35.6 36.7 29.1 38.3 36.5 38 12:36:04 34.1 35.5 36.6 29.2 38.3 36.5 38.1 12:36:09 34.1 35.5 36.6 29.2 38.3 36.5 38 12:36:13 34.1 35.5 36.6 29.2 38.3 36.5 38 12:36:17 34 35.5 36.6 29.2 38.3 36.5 38 12:36:21 34 35.5 36.6 29.2 38.3 36.5 38 12:36:25 34 35.5 36.6 29.3 38.3 36.5 37.9 12:36:29 34 35.5 36.5 28.9 38.3 36.5 38 12:36:34 34 35.5 36.5 29 38.3 36.5 38 12:36:38 34 35.5 36.5 29.1 38.3 36.5 38 12:36:42 33.9 35.4 36.5 29.1 38.3 36.5 38 12:36:46 33.9 35.4 36.5 29.2 38.3 36.5 38 12:36:50 33.9 35.3 36.5 29.2 38.3 36.5 38 12:36:54 33.8 35.4 36.5 29.2 38.3 36.5 38 12:36:58 33.8 35.3 36.5 29.2 38.2 36.5 38 12:37:03 33.8 35.4 36.5 29.2 38.3 36.5 38 12:37:07 33.8 35.3 36.5 29.2 38.3 36.4 38 12:37:11 33.8 35.3 36.5 29.2 38.3 36.5 38 12:37:15 33.8 35.3 36.4 29.2 38.2 36.4 37.9 12:37:19 33.8 35.3 36.5 29.3 38.3 36.5 38 12:37:23 33.8 35.3 36.4 29.2 38.3 36.5 38 12:37:28 33.8 35.3 36.4 29.2 38.2 36.5 37.9 12:37:32 33.8 35.3 36.4 29.2 38.2 36.4 37.9 12:37:36 33.7 35.2 36.3 29.2 38.2 36.4 37.9 12:37:40 33.7 35.2 36.4 29.2 38.2 36.4 38 12:37:44 33.7 35.2 36.4 29.2 38.2 36.5 38 12:37:48 33.7 35.2 36.3 29.2 38.2 36.4 37.9 12:37:53 33.7 35.2 36.3 28.7 38.3 36.4 37.9 12:37:57 33.7 35.2 36.3 28.7 38.2 36.4 37.9 12:38:01 33.7 35.2 36.3 28.7 38.3 36.5 37.9 12:38:05 33.7 35.2 36.3 28.7 38.3 36.5 38 12:38:09 33.6 35.2 36.3 28.6 38.2 36.4 37.9 12:38:13 33.6 35.2 36.3 28.6 38.2 36.4 37.9 12:38:17 33.6 35.2 36.2 28.6 38.2 36.4 37.8 12:38:21 33.6 35.2 36.3 28.6 38.2 36.5 37.9 12:38:25 33.6 35.2 36.3 28.6 38.3 36.5 37.9 12:38:30 33.6 35.1 36.2 28.5 38.2 36.4 37.8 12:38:34 33.6 35.2 36.2 28.5 38.3 36.4 37.9 12:38:38 33.6 35.1 36.2 28.5 38.2 36.4 37.8 12:38:42 33.6 35.1 36.1 28.4 38.2 36.3 37.8 12:38:46 33.6 35.1 36.2 28.3 38.2 36.4 37.8 12:38:50 33.6 35.1 36.2 28.4 38.2 36.5 37.9 12:38:55 33.6 35.1 36.2 28.3 38.2 36.4 37.9 12:38:59 33.6 35.1 36.1 28.4 38.2 36.4 37.8 12:39:03 33.6 35.1 36.2 28.3 38.2 36.4 37.8 12:39:07 33.5 35.1 36.1 28.3 38.2 36.3 37.8 12:39:11 33.6 35.1 36.1 28.3 38.2 36.3 37.8 12:39:15 33.6 35.1 36.1 28.3 38.2 36.4 37.8 12:39:19 33.6 35.1 36.1 28.3 38.2 36.4 37.8 12:39:24 33.5 35.1 36.1 28.2 38.2 36.3 37.8 12:39:28 33.6 35.1 36.1 28.2 38.2 36.4 37.8 12:39:32 33.5 35.1 36.1 28.1 38.2 36.3 37.8 12:39:36 33.6 35.1 36.1 28.2 38.2 36.4 37.8 12:39:40 33.5 35 36.1 28.1 38.2 36.3 37.8 12:39:44 33.6 35 36 28.1 38.2 36.3 37.8 12:39:49 33.6 35 36 28.1 38.2 36.3 37.8 12:39:53 33.5 35 36 28.1 38.2 36.3 37.8 12:39:57 33.5 35 36 28 38.2 36.3 37.8 12:40:01 33.5 35 36 28 38.2 36.3 37.8 12:40:05 33.5 35 36 27.9 38.2 36.3 37.8 12:40:09 33.5 35 36 28 38.2 36.3 37.8 12:40:13 33.5 35 36 27.9 38.2 36.3 37.8 12:40:18 33.5 35 36 27.9 38.2 36.3 37.8 12:40:22 33.5 35 36 27.9 38.2 36.3 37.8 12:40:26 33.5 35 36 27.9 38.2 36.3 37.8 12:40:30 33.5 35 36 27.9 38.2 36.3 37.7 12:40:34 33.5 35 36 27.9 38.2 36.3 37.7 12:40:38 33.5 35 35.9 27.8 38.2 36.3 37.7 12:40:42 33.5 35 36 27.8 38.2 36.3 37.7 12:40:47 33.5 35 35.9 27.8 38.1 36.3 37.8 12:40:51 33.5 35 36 27.7 38.2 36.3 37.7 12:40:55 33.6 34.9 35.9 27.8 38.2 36.3 37.8 12:40:59 33.5 34.9 35.9 27.8 38.2 36.3 37.7 12:41:03 33.5 34.9 35.9 27.7 38.2 36.3 37.7 12:41:07 33.5 34.9 35.9 27.8 38.2 36.3 37.7 12:41:12 33.6 34.9 35.9 27.7 38.2 36.3 37.7 12:41:16 33.5 34.9 35.9 27.7 38.2 36.3 37.7 12:41:20 33.5 34.9 35.9 27.6 38.2 36.3 37.7 12:41:24 33.6 34.9 35.8 27.6 38.1 36.3 37.7 12:41:28 33.5 34.9 35.8 27.6 38.1 36.3 37.7 12:41:32 33.6 34.9 35.8 27.6 38.1 36.3 37.7 12:41:36 33.5 34.8 35.8 27.6 38.1 36.2 37.7 12:41:41 33.6 34.9 35.8 27.6 38.1 36.3 37.7 12:41:45 33.5 34.8 35.8 27.7 38.1 36.2 37.7 12:41:49 33.6 34.8 35.8 27.7 38.1 36.3 37.7 12:41:53 33.6 34.8 35.8 27.8 38.1 36.3 37.7 12:41:57 33.6 34.9 35.8 28 38.1 36.3 37.7 12:42:01 33.6 35 35.8 28 38.1 36.3 37.7 12:42:05 33.7 35 35.7 28.6 38.1 36.3 37.7 12:42:10 33.7 35 35.8 28.3 38.1 36.3 37.7 12:42:14 33.7 35 35.7 28.2 38.1 36.2 37.7 12:42:18 33.8 35.1 35.8 28 38.1 36.2 37.7 12:42:22 33.8 35.1 35.8 27.8 38.1 36.3 37.7 12:42:26 33.9 35.1 35.7 27.7 38.1 36.3 37.7 12:42:30 33.9 35.1 35.7 27.6 38.1 36.2 37.7 12:42:35 34 35.1 35.8 27.6 38.1 36.3 37.7 12:42:39 34 35.1 35.7 27.5 38.1 36.3 37.7 12:42:43 34 35.1 35.8 27.5 38.1 36.3 37.7 12:42:47 34 35.1 35.7 27.4 38.1 36.3 37.7 12:42:51 34 35.1 35.7 27.3 38.1 36.2 37.7 12:42:55 34 35.1 35.7 27.2 38.1 36.3 37.7 12:42:59 34.1 35.1 35.8 27.2 38.1 36.3 37.7 12:43:04 34.1 35.1 35.8 27.2 38.1 36.3 37.7 12:43:08 34 35.1 35.7 27.2 38.1 36.2 37.6 12:43:12 34.1 35.1 35.7 27.3 38 36.2 37.6 12:43:16 34.1 35.1 35.7 27.5 38.1 36.2 37.6 12:43:20 34.2 35.2 35.7 27.5 38.1 36.2 37.6 12:43:24 34.3 35.3 35.7 27.6 38.1 36.2 37.6 12:43:28 34.3 35.5 35.7 27.6 38.1 36.2 37.6 12:43:33 34.4 35.5 35.7 27.5 38.1 36.2 37.6 12:43:37 34.5 35.5 35.7 27.5 38.1 36.2 37.6 12:43:41 34.7 35.5 35.7 27.4 38.1 36.2 37.6 12:43:45 34.7 35.5 35.8 27.4 38.1 36.2 37.6 12:43:49 34.7 35.5 35.8 27.4 38.1 36.2 37.6 12:43:53 34.7 35.5 35.8 27.3 38 36.2 37.6 12:43:58 34.7 35.4 35.7 27.4 38.1 36.2 37.6 12:44:02 34.8 35.5 35.8 27.4 38.1 36.2 37.6 12:44:06 34.8 35.6 35.8 27.5 38.1 36.2 37.6 12:44:10 34.8 35.6 35.8 27.5 38 36.2 37.6 12:44:14 34.9 35.6 35.8 27.5 38 36.2 37.6 12:44:18 35 35.6 35.8 27.5 38 36.2 37.6 12:44:22 35 35.6 35.8 27.6 38 36.2 37.6 12:44:27 35.1 35.7 35.8 27.7 38.1 36.2 37.6 12:44:31 35.1 35.6 35.8 27.7 38 36.2 37.6 12:44:35 35.1 35.7 35.8 27.7 38 36.2 37.6 12:44:39 35.1 35.6 35.8 27.7 38 36.2 37.5 12:44:43 35.1 35.6 35.9 27.8 38.1 36.2 37.5 12:44:47 35.1 35.6 35.9 27.8 38 36.2 37.6 12:44:52 35.1 35.6 35.8 27.7 38 36.2 37.6 12:44:56 35.1 35.7 35.8 27.6 38 36.1 37.5 12:45:00 35.1 35.7 35.8 27.6 38 36.2 37.6 12:45:04 35.2 35.7 35.9 27.5 38 36.2 37.6 12:45:08 35.2 35.7 35.9 27.6 38 36.2 37.6 12:45:12 35.2 35.8 35.8 27.5 38 36.2 37.6 12:45:17 35.2 35.8 35.8 27.5 38 36.2 37.5 12:45:21 35.2 35.8 35.9 27.5 38 36.1 37.6 12:45:25 35.3 35.8 35.9 27.5 38 36.1 37.6 12:45:29 35.3 35.8 35.9 27.5 38 36.1 37.5 12:45:33 35.3 35.8 35.9 27.5 38 36.2 37.6 12:45:37 35.3 35.8 36 27.5 38 36.2 37.6 12:45:41 35.3 35.7 35.9 27.5 38 36.1 37.5 12:45:46 35.2 35.7 35.9 27.6 38 36.1 37.5 12:45:50 35.2 35.7 36 27.6 38 36.1 37.6 12:45:54 35.2 35.7 35.9 27.6 38 36.1 37.5 12:45:58 35.2 35.7 36 27.6 38 36.1 37.5 12:46:02 35.3 35.8 35.9 27.6 38 36.1 37.5 12:46:06 35.3 35.8 36 27.6 38 36.1 37.5 12:46:10 35.3 35.8 36 27.6 38 36.2 37.5 12:46:15 35.3 35.8 35.9 27.6 38 36.1 37.5 12:46:19 35.3 35.9 36 27.8 38 36.1 37.5 12:46:23 35.3 35.9 36 27.7 38 36.1 37.5 12:46:27 35.4 35.9 36 27.7 38 36.2 37.6 12:46:31 35.4 35.9 36 27.6 38 36.1 37.5 12:46:35 35.5 35.9 36 27.5 38 36.1 37.5 12:46:40 35.5 35.9 36 27.5 38 36.1 37.5 12:46:44 35.5 35.9 36 27.5 38 36.1 37.5 12:46:48 35.5 35.9 36 27.5 38 36.1 37.5 12:46:52 35.5 36 36 27.5 38 36.1 37.5 12:46:56 35.5 35.9 36 27.5 38 36.1 37.5 12:47:00 35.5 36 36 27.4 38 36.1 37.4 12:47:04 35.5 35.9 36 27.3 38 36.1 37.5 12:47:08 35.5 35.9 36 27.3 38 36.1 37.5 12:47:13 35.5 35.9 36 27.2 38 36.1 37.5 12:47:17 35.5 35.9 36.1 27.1 38 36.1 37.5 12:47:21 35.5 35.9 36.1 27.1 38 36.1 37.4 12:47:25 35.5 35.9 36 27.1 38 36.1 37.5 12:47:29 35.5 36 36.1 27.1 38 36.1 37.4 12:47:33 35.5 35.9 36 27.1 38 36.1 37.4 12:47:37 35.5 36 36.1 27 38 36 37.4 12:47:42 35.5 36 36 27 38 36.1 37.4 12:47:46 35.5 36 36.1 27 38 36 37.4 12:47:50 35.5 35.9 36 27 38 36.1 37.5 12:47:54 35.5 36 36 26.8 38 36 37.4 12:47:58 35.6 36 36.1 26.9 38 36 37.4 12:48:02 35.6 36 36.1 26.8 38 36.1 37.4 12:48:07 35.6 36 36.1 26.9 37.9 36 37.4 12:48:11 35.6 36 36.1 26.9 38 36 37.4 12:48:15 35.6 36 36.1 26.9 38 36 37.4 12:48:19 35.5 36 36 26.9 37.9 36 37.3 12:48:23 35.5 35.9 36.1 26.9 38 36 37.3 12:48:27 35.5 36 36.1 26.9 38 36 37.4 12:48:32 35.5 36 36.1 27.2 37.9 36 37.4 12:48:36 35.5 36 36.1 27.3 38 36.1 37.4 12:48:40 35.5 35.9 36.1 27.1 37.9 36 37.3 12:48:44 35.5 36 36.1 27.2 38 36 37.4 12:48:48 35.5 36 36.1 27.5 37.9 36 37.3 12:48:52 35.5 36 36.1 27.5 38 36 37.4 12:48:56 35.5 35.9 36.1 27.5 37.9 36 37.3 12:49:00 35.5 36 36.1 27.6 37.9 36 37.3 12:49:05 35.5 35.9 36.1 27.4 37.9 36 37.3 12:49:09 35.5 36 36.1 27.1 37.9 36 37.3 12:49:13 35.5 35.9 36.1 27 38 36 37.3 12:49:17 35.5 35.9 36.1 26.8 37.9 36 37.3 12:49:21 35.4 35.9 36.1 26.8 37.9 36 37.3 12:49:25 35.4 35.9 36.1 26.8 37.9 36 37.3 12:49:30 35.4 35.8 36.1 26.8 37.9 36 37.3 12:49:34 35.3 35.8 36.1 26.7 37.9 36 37.3 12:49:38 35.3 35.8 36.1 26.6 37.9 36 37.3 12:49:42 35.3 35.8 36.1 26.5 37.9 36 37.3 12:49:46 35.3 35.8 36.1 26.3 37.9 36 37.3 12:49:50 35.3 35.8 36.1 26.2 37.9 36 37.3 12:49:55 35.3 35.8 36.1 26.1 37.9 36 37.3 12:49:59 35.3 35.8 36.1 25.9 37.9 36 37.3 12:50:03 35.2 35.8 36.1 25.9 37.9 36 37.3 12:50:07 35.2 35.8 36.1 26 37.9 36 37.3 12:50:11 35.2 35.8 36.1 26 37.9 36 37.3 12:50:15 35.2 35.7 36.1 25.8 37.9 36 37.3 12:50:20 35.1 35.7 36.1 25.7 37.9 36 37.3 12:50:24 35.1 35.7 36.1 25.7 37.9 35.9 37.2 12:50:28 35.1 35.7 36.1 25.7 37.8 36 37.3 12:50:32 35.1 35.7 36.1 25.6 37.8 35.9 37.3 12:50:36 35.1 35.7 36.1 25.6 37.8 35.9 37.2 12:50:40 35.1 35.7 36.1 25.7 37.9 36 37.3 12:50:44 35 35.7 36.1 25.6 37.9 36 37.3 12:50:49 35 35.6 36.1 25.7 37.9 36 37.2 12:50:53 35 35.6 36 25.7 37.8 35.9 37.2 12:50:57 35 35.6 36 25.6 37.8 35.9 37.2 12:51:01 34.9 35.6 36 25.7 37.8 35.9 37.2 12:51:05 34.9 35.6 36 25.7 37.8 35.8 37.2 12:51:10 34.8 35.6 36 25.7 37.8 35.9 37.2 12:51:14 34.8 35.6 36 25.7 37.8 35.9 37.2 12:51:18 34.8 35.6 36.1 25.7 37.9 35.9 37.2 12:51:22 34.8 35.6 36 25.7 37.8 36 37.3 12:51:26 34.8 35.5 36 25.6 37.8 35.9 37.3 12:51:30 34.8 35.5 36 25.5 37.8 35.9 37.2 12:51:34 34.8 35.5 36 25.5 37.8 35.9 37.2 12:51:39 34.7 35.5 36 25.5 37.8 35.9 37.2 12:51:43 34.7 35.5 36 25.6 37.8 35.9 37.2 12:51:47 34.7 35.5 36 25.6 37.8 35.9 37.2 12:51:51 34.7 35.5 36 25.6 37.8 35.8 37.2 12:51:55 34.7 35.5 36 25.6 37.8 35.9 37.2 12:51:59 34.7 35.5 36 25.6 37.8 35.8 37.2 12:52:04 34.7 35.5 36 25.6 37.8 35.9 37.2 12:52:08 34.7 35.5 36 25.6 37.8 35.9 37.2 12:52:12 34.7 35.5 36 25.6 37.8 35.8 37.2 12:52:16 34.7 35.4 36 25.6 37.8 35.9 37.2 12:52:20 34.7 35.4 36 25.5 37.8 35.8 37.2 12:52:24 34.7 35.4 36 25.5 37.8 35.8 37.2 12:52:28 34.6 35.5 36 25.5 37.8 35.8 37.2 12:52:32 34.6 35.4 35.9 25.5 37.8 35.9 37.2 12:52:37 34.6 35.4 35.9 25.5 37.8 35.8 37.2 12:52:41 34.6 35.4 35.9 25.5 37.8 35.8 37.2 12:52:45 34.6 35.3 35.9 25.5 37.8 35.8 37.2 12:52:49 34.6 35.4 35.9 25.5 37.8 35.9 37.2 12:52:53 34.6 35.4 35.9 25.5 37.8 35.8 37.1 12:52:58 34.6 35.3 35.9 25.4 37.8 35.8 37.2 12:53:02 34.6 35.3 35.9 25.6 37.8 35.8 37.2 12:53:06 34.6 35.3 35.9 25.5 37.8 35.8 37.1 12:53:10 34.6 35.4 35.9 25.5 37.8 35.8 37.1 12:53:14 34.6 35.3 35.9 25.5 37.8 35.8 37.2 12:53:18 34.6 35.3 35.9 25.6 37.8 35.8 37.2 12:53:22 34.6 35.3 35.8 25.6 37.8 35.8 37.2 12:53:27 34.6 35.3 35.9 25.6 37.8 35.8 37.2 12:53:31 34.6 35.3 35.9 25.7 37.8 35.8 37.2 12:53:35 34.6 35.3 35.8 25.7 37.8 35.8 37.1 12:53:39 34.6 35.3 35.9 25.6 37.8 35.8 37.2 12:53:43 34.6 35.3 35.8 25.6 37.8 35.8 37.2 12:53:47 34.6 35.3 35.8 25.6 37.8 35.8 37.1 12:53:51 34.6 35.3 35.8 25.6 37.8 35.8 37.1 12:53:55 34.6 35.3 35.8 25.5 37.8 35.8 37.1 12:54:00 34.6 35.3 35.8 25.6 37.8 35.8 37.2 12:54:04 34.6 35.3 35.8 25.5 37.8 35.8 37.2 12:54:08 34.6 35.3 35.8 25.4 37.7 35.8 37.1 12:54:12 34.6 35.3 35.8 25.5 37.8 35.8 37.1 12:54:16 34.6 35.3 35.8 25.4 37.8 35.8 37.1 12:54:20 34.6 35.3 35.8 25.4 37.7 35.8 37.1 12:54:24 34.6 35.3 35.8 25.4 37.8 35.8 37.1 12:54:29 34.6 35.3 35.8 25.5 37.7 35.8 37.1 12:54:33 34.6 35.4 35.7 25.5 37.7 35.8 37.1 12:54:37 34.7 35.3 35.8 25.6 37.7 35.8 37.1 12:54:41 34.6 35.3 35.8 26 37.7 35.8 37.1 TIME 1:VASC 1:AIRWAY 1:EAR MINUTES HEAD-M COOLING NOSE 12:26:52 37.7 30.3 32.3 0 38.1 0 26.6 12:26:56 37.7 30 32.3 0.066667 38.1 0 27.9 12:27:01 37.6 29.6 32.2 0.15 38.1 0 27 12:27:05 37.6 29.1 32.2 0.216667 38.1 0 15 12:27:09 37.6 28.9 32.3 0.283333 38.1 0 14 12:27:13 37.5 29.3 32.3 0.35 38.06667 −0.03333 12.8 12:27:17 37.3 29.8 32.3 0.416667 38 −0.1 12.9 12:27:21 37.3 30.1 32.3 0.483333 37.96667 −0.13333 12.6 12:27:26 37.1 29.7 32.3 0.566667 37.9 −0.2 11.8 12:27:30 37.1 29.4 32.3 0.633333 37.9 −0.2 12 12:27:34 37 29 32.3 0.7 37.83333 −0.26667 11.7 12:27:38 36.9 28.9 32.3 0.766667 37.8 −0.3 12 12:27:42 36.8 29.2 32.3 0.833333 37.73333 −0.36667 11.5 12:27:46 36.7 29.7 32.3 0.9 37.7 −0.4 11.7 12:27:50 36.7 29.7 32.3 0.966667 37.63333 −0.46667 11.8 12:27:55 36.7 29.6 32.3 1.05 37.6 −0.5 11.7 12:27:59 36.7 29.2 32.3 1.116667 37.53333 −0.56667 11.4 12:28:03 36.6 28.8 32.2 1.183333 37.53333 −0.56667 11.2 12:28:07 36.6 28.8 32.3 1.25 37.5 −0.6 11 12:28:11 36.5 29 32.3 1.316667 37.43333 −0.66667 10.8 12:28:15 36.6 29.5 32.3 1.383333 37.43333 −0.66667 10.8 12:28:20 36.7 29.8 32.3 1.466667 37.43333 −0.66667 11 12:28:24 36.8 29.6 32.3 1.533333 37.36667 −0.73333 11.2 12:28:28 36.9 29.3 32.3 1.6 37.26667 −0.83333 11.1 12:28:32 36.8 28.8 32.3 1.666667 37.33333 −0.76667 11.1 12:28:36 36.8 28.7 32.3 1.733333 37.26667 −0.83333 11.2 12:28:40 36.8 29 32.3 1.8 37.26667 −0.83333 11.1 12:28:44 36.7 29.5 32.3 1.866667 37.23333 −0.86667 11 12:28:49 36.8 29.9 32.3 1.95 37.2 −0.9 11.2 12:28:53 37 29.6 32.3 2.016667 37.13333 −0.96667 11.2 12:28:57 36.8 29.2 32.3 2.083333 37.1 −1 11.1 12:29:01 36.8 28.8 32.3 2.15 37.1 −1 11.2 12:29:05 36.8 29.2 32.3 2.216667 37.1 −1 11.2 12:29:09 36.8 29.2 32.3 2.283333 37.03333 −1.06667 11.3 12:29:13 36.6 29.6 32.3 2.35 37.03333 −1.06667 10.8 12:29:18 36.5 29.2 32.2 2.433333 37.06667 −1.03333 10.9 12:29:22 36.7 28.7 32.3 2.5 37.03333 −1.06667 10.5 12:29:26 36.5 28.5 32.3 2.566667 37.06667 −1.03333 10.8 12:29:30 36.6 28.6 32.3 2.633333 37 −1.1 10.8 12:29:34 36.5 29 32.3 2.7 37 −1.1 11 12:29:38 36.5 29.3 32.3 2.766667 36.96667 −1.13333 10.9 12:29:43 36.4 29.5 32.3 2.85 36.96667 −1.13333 10.9 12:29:47 36.5 29.2 32.3 2.916667 36.9 −1.2 10.8 12:29:51 36.7 28.8 32.3 2.983333 36.9 −1.2 10.9 12:29:55 36.7 28.5 32.3 3.05 36.9 −1.2 10.8 12:29:59 36.7 28.5 32.3 3.116667 36.83333 −1.26667 10.8 12:30:03 36.7 29 32.3 3.183333 36.86667 −1.23333 11.1 12:30:07 36.7 29.5 32.3 3.25 36.8 −1.3 10.9 12:30:12 36.7 29.4 32.3 3.333333 36.73333 −1.36667 10.9 12:30:16 36.7 29.1 32.3 3.4 36.76667 −1.33333 11 12:30:20 36.7 28.7 32.3 3.466667 36.73333 −1.36667 11.1 12:30:24 36.7 28.5 32.3 3.533333 36.7 −1.4 10.9 12:30:28 36.7 28.9 32.3 3.6 36.66667 −1.43333 11 12:30:32 36.6 29.4 32.3 3.666667 36.66667 −1.43333 11.1 2:30:36 36.7 29.5 32.3 3.733333 36.66667 −1.43333 11.1 12:30:41 36.7 29.1 32.3 3.816667 36.63333 −1.46667 10.8 12:30:45 36.7 28.7 32.3 3.883333 36.56667 −1.53333 11 12:30:49 36.7 28.4 32.3 3.95 36.56667 −1.53333 11.1 12:30:53 36.6 28.6 32.3 4.016667 36.56667 −1.53333 11 12:30:57 36.6 29.2 32.3 4.083333 36.56667 −1.53333 11 12:31:01 36.7 29.4 32.2 4.15 36.43333 −1.66667 11 12:31:06 36.7 29.2 32.3 4.233333 36.43333 −1.66667 11 12:31:10 36.7 28.7 32.2 4.3 36.46667 −1.63333 10.8 12:31:14 36.6 28.3 32.3 4.366667 36.46667 −1.63333 11 12:31:18 36.6 28.3 32.3 4.433333 36.46667 −1.63333 11 12:31:22 36.7 28.5 32.3 4.5 36.4 −1.7 11.1 12:31:26 36.7 29.1 32.2 4.566667 36.4 −1.7 11 12:31:30 36.7 29.2 32.3 4.633333 36.36667 −1.73333 11.3 12:31:35 36.6 28.9 32.2 4.716667 36.3 −1.8 11.3 12:31:39 36.7 28.5 32.2 4.783333 36.3 −1.8 11.2 12:31:43 36.7 28.2 32.2 4.85 36.3 −1.8 11.2 12:31:47 36.6 28.2 32.3 4.916667 36.3 −1.8 11.2 12:31:51 36.6 28.7 32.3 4.983333 36.3 −1.8 11 12:31:55 36.6 29.1 32.2 5.05 36.26667 −1.83333 10.9 12:31:59 36.5 29.1 32.2 5.116667 36.3 −1.8 11 12:32:04 36.6 28.7 32.2 5.2 36.2 −1.9 10.9 12:32:08 36.6 28.2 32.2 5.266667 36.2 −1.9 11 12:32:12 36.6 28 32.2 5.333333 36.2 −1.9 10.7 12:32:16 36.6 28.2 32.2 5.4 36.16667 −1.93333 11.3 12:32:20 36.6 28.7 32.2 5.466667 36.16667 −1.93333 11.1 12:32:24 36.6 29 32.2 5.533333 36.1 −2 10.8 12:32:29 36.6 28.7 32.2 5.616667 36.06667 −2.03333 10.8 12:32:33 36.5 28.3 32.2 5.683333 36.06667 −2.03333 10.7 12:32:37 36.6 28 32.2 5.75 36.06667 −2.03333 10.8 12:32:41 36.6 28 32.2 5.816667 36.03333 −2.06667 10.8 12:32:45 36.6 28.2 32.2 5.883333 36.03333 −2.06667 11 12:32:49 36.6 28.7 32.2 5.95 36 −2.1 11 12:32:53 36.6 28.9 32.2 6.016667 35.96667 −2.13333 11 12:32:58 36.7 28.7 32.2 6.1 35.96667 −2.13333 10.8 12:33:02 36.6 28.2 32.2 6.166667 35.93333 −2.16667 10.9 12:33:06 36.6 28.1 32.2 6.233333 35.93333 −2.16667 10.8 12:33:10 36.5 28.5 32.2 6.3 35.93333 −2.16667 10.8 12:33:14 36.6 29 32.2 6.366667 35.93333 −2.16667 10.6 12:33:18 36.6 29 32.2 6.433333 35.86667 −2.23333 10.9 12:33:23 36.7 28.8 32.2 6.516667 35.9 −2.2 10.8 12:33:27 36.7 28.4 32.2 6.583333 35.9 −2.2 10.8 12:33:31 36.7 28 32.2 6.65 35.86667 −2.23333 10.8 12:33:35 36.6 28.1 32.2 6.716667 35.86667 −2.23333 10.8 12:33:39 36.6 28.7 32.2 6.783333 35.83333 −2.26667 10.7 12:33:43 36.6 29 32.2 6.85 35.86667 −2.23333 11.1 12:33:47 36.6 28.7 32.2 6.916667 35.86667 −2.23333 10.8 12:33:52 36.6 28.4 32.2 7 35.86667 −2.23333 10.6 12:33:56 36.6 28.1 32.2 7.066667 35.86667 −2.23333 10.6 12:34:00 36.6 28 32.2 7.133333 35.9 −2.2 10.7 12:34:04 36.6 28.2 32.2 7.2 35.9 −2.2 10.7 12:34:08 36.5 28.6 32.2 7.266667 35.86667 −2.23333 10.7 12:34:12 36.6 29 32.2 7.333333 35.86667 −2.23333 10.7 12:34:16 36.5 28.8 32.2 7.4 35.86667 −2.23333 10.6 12:34:21 36.6 28.5 32.2 7.483333 35.83333 −2.26667 10.6 12:34:25 36.5 28.1 32.2 7.55 35.83333 −2.26667 10.4 12:34:29 36.5 28 32.2 7.616667 35.83333 −2.26667 10.6 12:34:33 36.5 28.2 32.2 7.683333 35.76667 −2.33333 10.6 12:34:37 36.4 28.6 32.2 7.75 35.76667 −2.33333 10.5 12:34:41 36.5 28.9 32.2 7.816667 35.76667 −2.33333 10.4 12:34:46 36.5 28.7 32.2 7.9 35.76667 −2.33333 10.5 12:34:50 36.5 28.4 32.2 7.966667 35.7 −2.4 10.7 12:34:54 36.4 28.2 32.2 8.033333 35.7 −2.4 10.5 12:34:58 36.3 27.9 32.2 8.1 35.7 −2.4 10.3 12:35:02 36.3 27.9 32.2 8.166667 35.66667 −2.43333 10.3 12:35:06 36.3 28.2 32.2 8.233333 35.7 −2.4 10.3 12:35:11 36.3 28.6 32.2 8.316667 35.63333 −2.46667 10.3 12:35:15 36.3 28.6 32.1 8.383333 35.6 −2.5 10.2 12:35:19 36.4 28.3 32.2 8.45 35.6 −2.5 10.3 12:35:23 36.3 28 32.2 8.516667 35.5 −2.6 10.3 12:35:27 36.3 27.8 32.1 8.583333 35.5 −2.6 10.2 12:35:31 36.3 27.8 32.1 8.65 35.5 −2.6 10.2 12:35:35 36.3 28.1 32.1 8.716667 35.53333 −2.56667 10.1 12:35:40 36.3 28.5 32.2 8.8 35.53333 −2.56667 10.1 12:35:44 36.3 28.6 32.2 8.866667 35.53333 −2.56667 9.9 12:35:48 36.4 28.5 32.2 8.933333 35.5 −2.6 10 12:35:52 36.5 28.2 32.2 9 35.46667 −2.63333 10 12:35:56 36.4 28 32.2 9.066667 35.4 −2.7 9.9 12:36:00 36.4 27.7 32.1 9.133333 35.46667 −2.63333 9.7 12:36:04 36.5 28.1 32.2 9.2 35.4 −2.7 9.9 12:36:09 36.4 28.4 32.2 9.283333 35.4 −2.7 9.8 12:36:13 36.3 28.6 32.1 9.35 35.4 −2.7 9.8 12:36:17 36.4 28.6 32.1 9.416667 35.36667 −2.73333 9.8 12:36:21 36.4 28.3 32.2 9.483333 35.36667 −2.73333 9.7 12:36:25 36.4 28 32.1 9.55 35.36667 −2.73333 9.8 12:36:29 36.4 27.8 32.2 9.616667 35.33333 −2.76667 9.7 12:36:34 36.4 27.8 32.1 9.7 35.33333 −2.76667 9.6 12:36:38 36.3 27.9 32.1 9.766667 35.33333 −2.76667 9.7 12:36:42 36.4 28.3 32.1 9.833333 35.26667 −2.83333 9.7 12:36:46 36.3 28.5 32.1 9.9 35.26667 −2.83333 9.6 12:36:50 36.3 28.3 32.1 9.966667 35.23333 −2.86667 9.5 12:36:54 36.3 28.1 32.1 10.03333 35.23333 −2.86667 9.6 12:36:58 36.3 27.8 32.1 10.1 35.2 −2.9 9.6 12:37:03 36.4 27.6 32.1 10.18333 35.23333 −2.86667 9.5 12:37:07 36.3 27.8 32.1 10.25 35.2 −2.9 9.5 12:37:11 36.3 28.2 32.1 10.31667 35.2 −2.9 9.6 12:37:15 36.3 28.2 32.1 10.38333 35.16667 −2.93333 9.6 12:37:19 36.3 28.1 32.1 10.45 35.2 −2.9 9.4 12:37:23 36.3 27.8 32.1 10.51667 35.16667 −2.93333 9.6 12:37:28 36.3 27.6 32.1 10.6 35.16667 −2.93333 9.6 12:37:32 36.3 27.7 32.1 10.66667 35.16667 −2.93333 9.3 12:37:36 36.2 28.1 32.1 10.73333 35.06667 −3.03333 9.4 12:37:40 36.2 28.3 32.1 10.8 35.1 −3 9.5 12:37:44 36.2 28.3 32.1 10.86667 35.1 −3 9.4 12:37:48 36.2 28 32.1 10.93333 35.06667 −3.03333 9.2 12:37:53 36.2 27.7 32.1 11.01667 35.06667 −3.03333 9.3 12:37:57 36.2 27.5 32.1 11.08333 35.06667 −3.03333 9.3 12:38:01 36.1 27.6 32.1 11.15 35.06667 −3.03333 9.3 12:38:05 36.1 28 32.1 11.21667 35.06667 −3.03333 9.3 12:38:09 36 28.2 32.1 11.28333 35.03333 −3.06667 9.3 12:38:13 36.1 28.1 32.1 11.35 35.03333 −3.06667 9.3 12:38:17 36 27.8 32.1 11.41667 35 −3.1 9.3 12:38:21 36.1 27.5 32.1 11.48333 35.03333 −3.06667 9.3 12:38:25 36.1 27.5 32.1 11.55 35.03333 −3.06667 9.3 12:38:30 36 27.7 32.1 11.63333 34.96667 −3.13333 9.3 12:38:34 36 28.1 32.1 11.7 35 −3.1 9.3 12:38:38 36.1 28.1 32.1 11.76667 34.96667 −3.13333 9.3 12:38:42 36.1 27.8 32.1 11.83333 34.93333 −3.16667 9.4 12:38:46 36.1 27.5 32.1 11.9 34.96667 −3.13333 9.5 12:38:50 36.2 27.3 32.1 11.96667 34.96667 −3.13333 9.4 12:38:55 36 27.5 32.1 12.05 34.96667 −3.13333 9.4 12:38:59 36.1 27.8 32.1 12.11667 34.93333 −3.16667 9.5 12:39:03 36.1 28.2 32.1 12.18333 34.96667 −3.13333 9.5 12:39:07 36.1 28.1 32.1 12.25 34.9 −3.2 9.4 12:39:11 36.1 27.8 32.1 12.31667 34.93333 −3.16667 9.4 12:39:15 36.1 27.5 32.1 12.38333 34.93333 −3.16667 9.5 12:39:19 36.1 27.3 32.1 12.45 34.93333 −3.16667 9.6 12:39:24 36 27.6 32.1 12.53333 34.9 −3.2 9.4 12:39:28 36.1 28 32.1 12.6 34.93333 −3.16667 9.3 12:39:32 36 28.2 32 12.66667 34.9 −3.2 9.5 12:39:36 36 28.1 32.1 12.73333 34.93333 −3.16667 9.5 12:39:40 36 27.8 32.1 12.8 34.86667 −3.23333 9.3 12:39:44 36.1 27.5 32 12.86667 34.86667 −3.23333 9.3 12:39:49 36.1 27.3 32 12.95 34.86667 −3.23333 9.3 12:39:53 36 27.6 32 13.01667 34.83333 −3.26667 9.3 12:39:57 36.1 28 32 13.08333 34.83333 −3.26667 9.2 12:40:01 36 28.1 32 13.15 34.83333 −3.26667 9.2 12:40:05 36 27.8 32 13.21667 34.83333 −3.26667 9.2 12:40:09 36.1 27.5 32 13.28333 34.83333 −3.26667 9.2 12:40:13 36.2 27.3 32.1 13.35 34.83333 −3.26667 9.2 12:40:18 36 27.3 32 13.43333 34.83333 −3.26667 9.1 12:40:22 36 27.8 32 13.5 34.83333 −3.26667 9.2 12:40:26 36 28.1 32 13.56667 34.83333 −3.26667 9.1 12:40:30 36 27.9 32 13.63333 34.83333 −3.26667 9.1 12:40:34 36 27.7 32 13.7 34.83333 −3.26667 9.1 12:40:38 36 27.3 32 13.76667 34.8 −3.3 9.2 12:40:42 36 27.2 32 13.83333 34.83333 −3.26667 9 12:40:47 36 27.5 32 13.91667 34.8 −3.3 8.9 12:40:51 35.9 27.9 32 13.98333 34.83333 −3.26667 8.8 12:40:55 35.9 28 32 14.05 34.8 −3.3 8.9 12:40:59 35.9 27.6 32 14.11667 34.76667 −3.33333 8.9 12:41:03 36 27.3 32 14.18333 34.76667 −3.33333 8.8 12:41:07 35.9 27.1 32 14.25 34.76667 −3.33333 8.8 12:41:12 36 27.4 32 14.33333 34.8 −3.3 8.8 12:41:16 36 28 32 14.4 34.76667 −3.33333 8.8 12:41:20 35.9 27.7 32 14.46667 34.76667 −3.33333 8.8 12:41:24 36 27.4 32 14.53333 34.76667 −3.33333 8.7 12:41:28 36 27.1 32 14.6 34.73333 −3.36667 8.8 12:41:32 35.8 27.2 32 14.66667 34.76667 −3.33333 8.8 12:41:36 35.8 27.7 32 14.73333 34.7 −3.4 8.9 12:41:41 35.9 27.9 32 14.81667 34.76667 −3.33333 8.8 12:41:45 35.9 27.7 32 14.88333 34.7 −3.4 8.8 12:41:49 35.8 27.4 32 14.95 34.73333 −3.36667 8.8 12:41:53 35.9 27.1 32 15.01667 34.73333 −3.36667 8.8 12:41:57 35.8 27.1 32 15.08333 34.76667 −3.33333 9 12:42:01 35.8 27.5 32 15.15 34.8 −3.3 8.8 12:42:05 35.7 27.8 32 15.21667 34.8 −3.3 8.8 12:42:10 35.9 27.6 32 15.3 34.83333 −3.26667 8.7 12:42:14 35.8 27.3 32 15.36667 34.8 −3.3 8.8 12:42:18 35.8 27 32 15.43333 34.9 −3.2 8.8 12:42:22 35.8 27.1 32 15.5 34.9 −3.2 8.8 12:42:26 35.8 27.3 32 15.56667 34.9 −3.2 8.6 12:42:30 35.8 27.7 32 15.63333 34.9 −3.2 8.5 12:42:35 35.9 27.7 32 15.71667 34.96667 −3.13333 8.6 12:42:39 35.9 27.5 32 15.78333 34.93333 −3.16667 8.5 12:42:43 35.8 27.1 32 15.85 34.96667 −3.13333 8.5 12:42:47 35.7 27 32 15.91667 34.93333 −3.16667 8.5 12:42:51 35.8 27.2 32 15.98333 34.93333 −3.16667 9.2 12:42:55 35.8 27.6 32 16.05 34.93333 −3.16667 9.1 12:42:59 35.8 27.7 32 16.11667 35 −3.1 9.1 12:43:04 35.9 27.5 32 16.2 35 −3.1 8.9 12:43:08 35.8 27.2 31.9 16.26667 34.93333 −3.16667 8.9 12:43:12 35.7 26.8 31.9 16.33333 34.96667 −3.13333 8.9 12:43:16 35.6 27 32 16.4 34.96667 −3.13333 8.9 12:43:20 35.7 27.4 32 16.46667 35.03333 −3.06667 8.7 12:43:24 35.7 27.8 31.9 16.53333 35.1 −3 8.7 12:43:28 35.8 27.5 31.9 16.6 35.16667 −2.93333 8.7 12:43:33 35.8 27.3 31.9 16.68333 35.2 −2.9 8.8 12:43:37 35.8 27.1 31.9 16.75 35.23333 −2.86667 8.7 12:43:41 35.7 26.8 31.9 16.81667 35.3 −2.8 8.7 12:43:45 35.7 27.1 31.9 16.88333 35.33333 −2.76667 8.7 12:43:49 35.8 27.5 31.9 16.95 35.33333 −2.76667 8.8 12:43:53 35.7 27.6 31.9 17.01667 35.33333 −2.76667 8.7 12:43:58 35.6 27.5 31.9 17.1 35.26667 −2.83333 8.9 12:44:02 35.8 27.1 32 17.16667 35.36667 −2.73333 8.8 12:44:06 35.7 26.9 32 17.23333 35.4 −2.7 8.8 12:44:10 35.6 26.8 31.9 17.3 35.4 −2.7 8.8 12:44:14 35.5 27.2 31.9 17.36667 35.43333 −2.66667 8.7 12:44:18 35.6 27.5 31.9 17.43333 35.46667 −2.63333 8.7 12:44:22 35.8 27.6 31.9 17.5 35.46667 −2.63333 8.7 12:44:27 35.8 27.3 31.9 17.58333 35.53333 −2.56667 8.6 12:44:31 35.8 27.1 31.9 17.65 35.5 −2.6 8.6 12:44:35 35.8 26.8 31.9 17.71667 35.53333 −2.56667 8.6 12:44:39 35.7 26.8 31.8 17.78333 35.5 −2.6 8.4 12:44:43 35.6 27.2 31.8 17.85 35.53333 −2.56667 8.5 12:44:47 35.7 27.5 31.9 17.91667 35.53333 −2.56667 8.5 12:44:52 35.8 27.5 31.8 18 35.5 −2.6 8.6 12:44:56 35.7 27.1 31.8 18.06667 35.53333 −2.56667 8.8 12:45:00 35.5 26.8 31.9 18.13333 35.53333 −2.56667 8.8 12:45:04 35.6 27 31.8 18.2 35.6 −2.5 8.7 12:45:08 35.7 27.4 31.8 18.26667 35.6 −2.5 8.5 12:45:12 35.7 27.5 31.8 18.33333 35.6 −2.5 8.5 12:45:17 35.7 27.3 31.8 18.41667 35.6 −2.5 8.5 12:45:21 35.7 27 31.8 18.48333 35.63333 −2.46667 8.5 12:45:25 35.6 26.7 31.8 18.55 35.66667 −2.43333 8.3 12:45:29 35.5 26.8 31.8 18.61667 35.66667 −2.43333 8.4 12:45:33 35.6 27.4 31.8 18.68333 35.66667 −2.43333 8.6 12:45:37 35.8 27.5 31.8 18.75 35.7 −2.4 8.5 12:45:41 35.7 27.2 31.8 18.81667 35.63333 −2.46667 8.5 12:45:46 35.6 27 31.8 18.9 35.6 −2.5 8.6 12:45:50 35.6 26.7 31.8 18.96667 35.63333 −2.46667 8.6 12:45:54 35.7 26.8 31.7 19.03333 35.6 −2.5 8.5 12:45:58 35.7 27.3 31.8 19.1 35.63333 −2.46667 8.5 12:46:02 35.7 27.6 31.8 19.16667 35.66667 −2.43333 8.5 12:46:06 35.6 27.3 31.8 19.23333 35.7 −2.4 8.6 12:46:10 35.6 27 31.8 19.3 35.7 −2.4 8.5 12:46:15 35.6 26.8 31.8 19.38333 35.66667 −2.43333 8.3 12:46:19 35.7 26.9 31.8 19.45 35.73333 −2.36667 8.4 12:46:23 35.6 27.2 31.8 19.51667 35.73333 −2.36667 8.4 12:46:27 35.7 27.6 31.8 19.58333 35.76667 −2.33333 8.5 12:46:31 35.7 27.4 31.8 19.65 35.76667 −2.33333 8.5 12:46:35 35.6 27.2 31.8 19.71667 35.8 −2.3 8.4 12:46:40 35.5 26.9 31.8 19.8 35.8 −2.3 8.3 12:46:44 35.6 26.7 31.8 19.86667 35.8 −2.3 8.2 12:46:48 35.6 27.1 31.8 19.93333 35.8 −2.3 8.2 12:46:52 35.6 27.5 31.8 20 35.83333 −2.26667 8.1 12:46:56 35.6 27.5 31.8 20.06667 35.8 −2.3 8.1 12:47:00 35.7 27.2 31.8 20.13333 35.83333 −2.26667 8.2 12:47:04 35.7 27 31.8 20.2 35.8 −2.3 8.3 12:47:08 35.7 26.7 31.8 20.26667 35.8 −2.3 8.2 12:47:13 35.6 27 31.8 20.35 35.8 −2.3 8.1 12:47:17 35.7 27.2 31.8 20.41667 35.83333 −2.26667 8.1 12:47:21 35.6 27.5 31.8 20.48333 35.83333 −2.26667 8.2 12:47:25 35.5 27.3 31.8 20.55 35.8 −2.3 8.4 12:47:29 35.6 27.1 31.8 20.61667 35.86667 −2.23333 8.3 12:47:33 35.7 26.8 31.8 20.68333 35.8 −2.3 8.3 12:47:37 35.7 26.7 31.8 20.75 35.86667 −2.23333 8.2 12:47:42 35.7 27 31.8 20.83333 35.83333 −2.26667 8.2 12:47:46 35.7 27.3 31.8 20.9 35.86667 −2.23333 8.2 12:47:50 35.7 27.5 31.8 20.96667 35.8 −2.3 8.2 12:47:54 35.7 27.5 31.8 21.03333 35.83333 −2.26667 8.2 12:47:58 35.7 27.2 31.8 21.1 35.9 −2.2 8.2 12:48:02 35.6 26.9 31.8 21.16667 35.9 −2.2 8.2 12:48:07 35.6 26.7 31.8 21.25 35.9 −2.2 8.2 12:48:11 35.5 26.8 31.8 21.31667 35.9 −2.2 8.1 12:48:15 35.5 27.1 31.8 21.38333 35.9 −2.2 8.2 12:48:19 35.6 27.5 31.8 21.45 35.83333 −2.26667 8.1 12:48:23 35.6 27.3 31.8 21.51667 35.83333 −2.26667 8.1 12:48:27 35.6 27.1 31.8 21.58333 35.86667 −2.23333 8.2 12:48:32 35.6 26.8 31.8 21.66667 35.86667 −2.23333 11.1 12:48:36 35.5 26.7 31.8 21.73333 35.86667 −2.23333 12.8 12:48:40 35.5 27.3 31.8 21.8 35.83333 −2.26667 12.7 12:48:44 35.5 27.6 31.8 21.86667 35.86667 −2.23333 13.2 12:48:48 35.5 27.4 31.7 21.93333 35.86667 −2.23333 13.8 12:48:52 35.6 27 31.7 22 35.86667 −2.23333 14 12:48:56 35.5 26.7 31.7 22.06667 35.83333 −2.26667 14.5 12:49:00 35.5 26.7 31.7 22.13333 35.86667 −2.23333 10 12:49:05 35.3 27.1 31.7 22.21667 35.83333 −2.26667 9.6 12:49:09 35.4 27.5 31.7 22.28333 35.86667 −2.23333 8.9 12:49:13 35.6 27.3 31.7 22.35 35.83333 −2.26667 8.6 12:49:17 35.5 27.2 31.7 22.41667 35.83333 −2.26667 8.5 12:49:21 35.5 26.9 31.8 22.48333 35.8 −2.3 8.6 12:49:25 35.5 26.8 31.8 22.55 35.8 −2.3 8.5 12:49:30 35.5 27.2 31.7 22.63333 35.76667 −2.33333 8.4 12:49:34 35.5 27.6 31.7 22.7 35.73333 −2.36667 8.4 12:49:38 35.5 27.5 31.7 22.76667 35.73333 −2.36667 8.5 12:49:42 35.6 27.4 31.7 22.83333 35.73333 −2.36667 8.4 12:49:46 35.6 27 31.7 22.9 35.73333 −2.36667 8.3 12:49:50 35.6 26.8 31.7 22.96667 35.73333 −2.36667 8.3 12:49:55 35.6 27 31.7 23.05 35.73333 −2.36667 8.3 12:49:59 35.5 27.4 31.7 23.11667 35.73333 −2.36667 8.4 12:50:03 35.5 27.6 31.7 23.18333 35.7 −2.4 8.4 12:50:07 35.5 27.5 31.7 23.25 35.7 −2.4 8.3 12:50:11 35.6 27.2 31.7 23.31667 35.7 −2.4 8.3 12:50:15 35.5 26.8 31.7 23.38333 35.66667 −2.43333 8.3 12:50:20 35.5 26.8 31.7 23.46667 35.63333 −2.46667 8.3 12:50:24 35.5 27.2 31.7 23.53333 35.63333 −2.46667 8.3 12:50:28 35.5 27.6 31.7 23.6 35.63333 −2.46667 8.2 12:50:32 35.5 27.5 31.7 23.66667 35.63333 −2.46667 8.2 12:50:36 35.5 27.3 31.7 23.73333 35.63333 −2.46667 8.3 12:50:40 35.5 27 31.7 23.8 35.63333 −2.46667 8.3 12:50:44 35.5 26.8 31.7 23.86667 35.6 −2.5 8.2 12:50:49 35.5 27.1 31.7 23.95 35.56667 −2.53333 8.5 12:50:53 35.3 27.5 31.6 24.01667 35.53333 −2.56667 8.3 12:50:57 35.3 27.5 31.6 24.08333 35.53333 −2.56667 8.3 12:51:01 35.5 27.3 31.6 24.15 35.5 −2.6 8.2 12:51:05 35.5 27 31.7 24.21667 35.5 −2.6 8.2 12:51:10 35.4 26.8 31.7 24.3 35.46667 −2.63333 8.2 12:51:14 35.3 26.9 31.7 24.36667 35.46667 −2.63333 8.2 12:51:18 35.3 27.3 31.7 24.43333 35.5 −2.6 8.1 12:51:22 35.4 27.6 31.7 24.5 35.46667 −2.63333 8.2 12:51:26 35.3 27.4 31.6 24.56667 35.43333 −2.66667 8.2 12:51:30 35.3 27.1 31.7 24.63333 35.43333 −2.66667 8.2 12:51:34 35.3 26.9 31.7 24.7 35.43333 −2.66667 8.1 12:51:39 35.3 26.8 31.7 24.78333 35.4 −2.7 8.1 12:51:43 35.3 27.1 31.6 24.85 35.4 −2.7 8 12:51:47 35.3 27.5 31.7 24.91667 35.4 −2.7 8 12:51:51 35.3 27.5 31.6 24.98333 35.4 −2.7 8 12:51:55 35.3 27.2 31.6 25.05 35.4 −2.7 8 12:51:59 35.3 27.1 31.7 25.11667 35.4 −2.7 8.1 12:52:04 35.3 26.8 31.6 25.2 35.4 −2.7 8 12:52:08 35.3 26.9 31.6 25.26667 35.4 −2.7 8 12:52:12 35.3 27.3 31.6 25.33333 35.4 −2.7 8.1 12:52:16 35.3 27.6 31.7 25.4 35.36667 −2.73333 8.1 12:52:20 35.3 27.4 31.6 25.46667 35.36667 −2.73333 8.1 12:52:24 35.3 27.1 31.6 25.53333 35.36667 −2.73333 8 12:52:28 35.2 26.8 31.6 25.6 35.36667 −2.73333 8 12:52:32 35.3 27.1 31.6 25.66667 35.3 −2.8 8.1 12:52:37 35.3 27.5 31.6 25.75 35.3 −2.8 8.1 12:52:41 35.2 27.4 31.6 25.81667 35.3 −2.8 8.1 12:52:45 35.3 27.2 31.6 25.88333 35.26667 −2.83333 8 12:52:49 35.3 26.9 31.6 25.95 35.3 −2.8 8 12:52:53 35.2 26.8 31.6 26.01667 35.3 −2.8 8.1 12:52:58 35.2 27 31.6 26.1 35.26667 −2.83333 8 12:53:02 35.2 27.4 31.6 26.16667 35.26667 −2.83333 7.9 12:53:06 35.3 27.5 31.6 26.23333 35.26667 −2.83333 7.9 12:53:10 35.3 27.4 31.6 26.3 35.3 −2.8 8.1 12:53:14 35.3 27.1 31.6 26.36667 35.26667 −2.83333 8 12:53:18 35.2 26.9 31.6 26.43333 35.26667 −2.83333 8 12:53:22 35.2 26.8 31.6 26.5 35.23333 −2.86667 8 12:53:27 35.2 27.1 31.6 26.58333 35.26667 −2.83333 8 12:53:31 35.2 27.5 31.6 26.65 35.26667 −2.83333 7.9 12:53:35 35.2 27.5 31.6 26.71667 35.23333 −2.86667 8 12:53:39 35.2 27.3 31.6 26.78333 35.26667 −2.83333 8 12:53:43 35.2 27 31.6 26.85 35.23333 −2.86667 8 12:53:47 35.1 26.8 31.6 26.91667 35.23333 −2.86667 8 12:53:51 35.3 26.9 31.6 26.98333 35.23333 −2.86667 8 12:53:55 35.4 27.2 31.6 27.05 35.23333 −2.86667 7.9 12:54:00 35.5 27.5 31.6 27.13333 35.23333 −2.86667 8 12:54:04 35.4 27.4 31.6 27.2 35.23333 −2.86667 8 12:54:08 35.4 27.1 31.6 27.26667 35.23333 −2.86667 7.8 12:54:12 35.4 26.8 31.6 27.33333 35.23333 −2.86667 7.8 12:54:16 35.1 26.8 31.6 27.4 35.23333 −2.86667 7.8 12:54:20 35 27.1 31.6 27.46667 35.23333 −2.86667 8 12:54:24 35 27.5 31.6 27.53333 35.23333 −2.86667 8 12:54:29 34.8 27.5 31.6 27.61667 35.23333 −2.86667 7.8 12:54:33 34.8 27.3 31.6 27.68333 35.23333 −2.86667 7.8 12:54:37 34.9 27 31.6 27.75 35.26667 −2.83333 7.4 12:54:41 35 26.8 31.6 27.81667 35.23333 −2.86667 8.7
(115)
(116)
(117)
(118)
(119)
(120) Nasal catheter 910 is connected to mixing catheter 914 by a connecting tube 916. Connecting tube 916 is a hollow, open ended tube for attaching nasal catheter 910 to mixing catheter 914 and for placing nasal catheter 910 in fluid communication with at least the lower lumen 920 of mixing catheter 914. It can be made from metal ‘hypodermic’ tubing, or a suitable plastic. As shown in
(121) At this point, the gas is moving at a high velocity, and the liquid experiences high shear forces, breaking the stream into small droplets that then flow through the lumen of nasal catheter 910 and are delivered as a spray to the patient's nasal cavity through the spray nozzle 915.
(122)
(123)
(124)
(125)
(126) Expandable members 992a-b and 991a-b at the distal and proximal ends of catheter 990 prevent non-vaporized fluid from leaking into the throat or running out the patient's nostrils. The non-vaporized liquid may then be suctioned from the nasal cavity via suction lumen 999, which is in fluid communication with port 998. This liquid may be discarded or alternatively it may be recycled for successive use. Because there is a dedicated lumen for delivery and suction, however, delivery of the cooled liquid to the nasal cavity does not need to be interrupted.
(127) Convective Cooling in the Nasal Cavity
(128) In another aspect of this invention, a catheter with a flexible balloon having a chamber filled with a cooling liquid can be used to cool the brain via the nasal cavity. As seen in
(129) In use, as seen in
(130) In an alternative embodiment, a flexible balloon having a chamber filled with a cooling liquid can be used to cool the brain via the nasal cavity. As seen in
(131) In use, as seen in
(132) In an alternative embodiment, a flexible balloon having a chamber filled with a cooling liquid can be used to cool the brain via the nasal cavity. As seen in
(133) In use, assembly 700 is inserted into the nasal cavity through a nostril such that flexible balloon 702 is within the nasal cavity. A cooling fluid can then be used to inflate flexible balloon 702 to a sufficient pressure such that flexible balloon 702 expands and is in contact with a substantial portion of the nasal cavity. The cooling fluid is then recirculated through flexible balloon 702 via lumens 706, 716, and 721, cooler 722, and pump 724. For instance, cooling liquid may be withdrawn from chamber 703 by having pump 722 withdraw the cooling liquid through lumens 706 and 721 of elongate tubular members 708 and 720, respectively. Cooling liquid can then be pumped into cooler for further cooling and then pumped back into chamber 703 through lumens 716 and 706 of elongate tubular members 715 and 708. In order to optimize cooling and minimize tissue damage, it may be desirable to continuously inflate and deflate flexible balloon 702. Additionally, a second assembly can also be inserted into the other nostril such that maximum cooling can be obtained. The cooling of the brain would occur by convection or heat exchange from the cold liquid in the balloon to the warm nasal cavity.
(134) In an alternative embodiment, a flexible balloon having a chamber filled with a cooling liquid and a cold finger inside of a second balloon can be used to cool the brain via the nasal cavity. As seen in
(135) Cold probe 607 may also have fins surrounding the cold probe (not shown) to increase the surface area of the probe. Alternatively, a heat pipe could be used in place of the cold probe. The heat pipe could be filled with a gas such as Freon or ammonia, or alternatively, the heat pipe could be connected to a circulating cooling liquid reservoir or other cooling source (such as a block of ice).
(136) In use, assembly 600 is inserted into the nasal cavity through the patient's nostril such that flexible balloon 602 is within the nasal cavity. A cooling fluid can then be used in inflate flexible balloon 602 to a sufficient pressure such that flexible balloon 602 expands and is in contact with a substantial portion of the nasal cavity. The cooling agent will then be circulated into second balloon 605 via port 608 at the distal end of cold probe 607 and elongate tubular member 614. Alternatively, the cooling agent may not be recirculated, but rather be vented out of a port in second balloon 605 (not shown). Additionally, the fluid in the balloon can be agitated to prevent freezing. This may be accomplished by moving cold probe 607 or pulsing the infusion of the cooling agent into second balloon 605. Additionally, a second assembly can also be inserted into the other nostril such that maximum cooling can be obtained. The cooling of the brain would occur by convection or heat exchange from the cold liquid in the balloon to the warm nasal cavity.
(137) In an alternative embodiment, a flexible balloon having a chamber filled with a cooling liquid and a cold finger can be used to cool the brain via the nasal cavity. As seen in
(138) In use, with the patient lying on his back, assembly 650 is inserted into the nasal cavity through the patient's nostril such that flexible balloon 652 is within nasal cavity 670. A cooling fluid can then be used in inflate flexible balloon 652 to a sufficient pressure such that flexible balloon 652 expands and is in contact with a substantial portion of nasal cavity 670. The cooling agent will flow out of port 658 of cold probe 657 and produce gas bubbles 660 in the cooling liquid in chamber 653, thereby cooling the liquid further and agitating the liquid to aid in mixing the liquid throughout chamber 653. The gas bubbles can exit chamber 653 through port 654 with air venting filter 656, which allows for the release of gas and not liquid. Additionally, the fluid in the balloon can be agitated to prevent freezing. This may be accomplished by moving cold probe 657 or pulsing the infusion of the cooling agent into chamber 653. Additionally, a second assembly can also be inserted into the other nostril such that maximum cooling can be obtained. The cooling of the brain would occur by convection or heat exchange from the cold liquid in the balloon to the warm nasal cavity.
(139) Flexible balloons for use in the nasal cavity are sized such that upon inflation, they are capable of making good contact with the surfaces of the nasal cavity, including the portion of the cavity that lies posterior to the cavernous sinus. In one embodiment, the length of the flexible balloon will depend upon the size of the nasal cavity and may be less than 15 cm long, alternatively less than 14 cm long, alternatively less than 13 cm long, alternatively less than 12 cm long, alternatively less than 11 cm long, alternatively less than 10 cm long, alternatively less than 9 cm long, alternatively less than 8 cm long. The flexible balloons may also have the shape of the nasal cavity. Alternatively, as seen in
(140) In use, the pressure in these flexible balloons for use in the nasal cavity can oscillate between lower and higher pressures. In other words, the fluid can be infused to fill the chamber defined by the balloon either slowly or quickly. When expanded at higher pressures, presumably more heat transfer will occur due to increased contact with the nasal cavity. Extended periods at higher pressures, however, may not be desirable due to possible problems with stopping blood flow in the surrounding tissue. Additionally, the act of pulsing the liquid would result in increased circulation of the liquid. Rapid pulsing, for the purposes of mixing the liquid within the balloon chamber, could range from about 0.5 to about 200 Hz, alternatively from about 1 to about 150 Hz, alternatively from about 1 to about 100 Hz, alternatively from about 10 to about 100 Hz, alternatively from about 25 to about 100 Hz. Slower pulsing could be used to effect physiologic responses, such as deflating the balloon to allow blood flow to resume circulation in the cooled area. Slower pulsing could range from about one inflation per second to about one inflation per 10 minutes, alternatively from about one inflation per second to about one inflation per 5 minutes, alternatively from about one inflation per second to about one inflation per 3 minutes. Alternatively, the balloon could be inflated approximately once every 30 seconds, alternatively once every 1 minute, alternatively once every 2 minutes, alternatively once every 3 minutes, alternatively once every 4 minutes, alternatively once every 5 minutes, alternatively once every 6 minutes, alternatively once every 7 minutes, alternatively once every 8 minutes, alternatively once every 9 minutes, alternatively once every 10 minutes. During these slower cycling periods, the balloon could remain inflated for approximately 1% of the cycling period, alternatively approximately 5% of the cycling period, alternatively approximately 10% of the cycling period, alternatively approximately 20% of the cycling period, alternatively approximately 30% of the cycling period, alternatively approximately 40% of the cycling period, alternatively approximately 50% of the cycling period.
(141) Cooling Calculations
(142) The following calculations estimate the maximum cooling that can be obtained when a chilled liquid is circulated through the nasal cavity, where the chilled fluid is either directly in contact with the nasal tissues or contained in a flexible membrane ‘balloon’ within the nose.
(143) A cooling liquid is circulated into and out of the nasal cavity. The following calculations are done assuming that the chilled fluid will be an aqueous fluid. The following are properties of water: Density: 1 gram/ml Heat capacity: 1 cal/gram-° C.
(144) The liquid will enter the nasal cavity at a temperature well below body temperature, and exit at a warmer temperature. The warming of the water will be equal to the cooling of the body, so the calculations for heat added to the water is the same as that for heat removed from the body.
Q′=c*m*(T2−T1) or Q′=cmΔT Equation 1: Q′=the rate of heat transfer m=the mass flow rate of the liquid administered c=the heat capacity of the liquid T1=the temperature of the liquid at administration T2=the temperature to which the liquid is warmed
(145) If the flow rate is 500 ml/min, inlet temperature is 2° C., outlet temperature is 4° C.
Heat Transfer=500 ml/min*1 g/ml*1 cal/gm° C.*(4° C.−2° C.)=1000 cal/min Conversion factors: 1 calorie/minute=0.069 78 watt 1000 cal/min*0.06978 Watt/cal/min=70 Watts
(146) The cooling of the whole body can be calculated using the same equation as above. The heat capacity of the human body is generally accepted to be 0.85 cal/gm ° C. For this calculation, other sources of heat entering or leaving the body, and heat generated in the body are neglected, as it is likely those aspects balance out in a stable patient. Cooling therefore reduces to the equation below.
Whole body cooling(ΔT)=Heat removed/(mass*heat capacity)
(147) Continuing the example above, for a 75 kg patient, the temperature change is calculated below to be 0.93° C. per hour, which is close to the target cooling rate for patients.
(148)
(149) For whole body cooling (WBC), the following formula can be developed from the above:
WBC(° C./hr)=ΔT(liquid,° C.)*Flow rate (ml/min)/(Patient wt (kg)*14.3)
or
WBC(° C./hr)=Cooling (watts)/Patient Weight (kg)
(150) The surface of the balloon may be treated or modified to maximize thermal conductance. A gel may also be optionally applied to the exterior of flexible balloons 204, 254 before insertion into the nasal cavity. The gel would preferably have good thermal conduction properties and be a better conductor than air. Additionally, the gel could also act as a lubricant to assist in the insertion. The gel may include, but is not limited to, any aqueous gel, a poloxamer-based gel, a cellulose gel (such as KY jelly), a nasal-packing jelly, or a thermal gel. Alternatively, sponges may be attached to the surface of the balloon. Sponges, such as PVA sponges, are commonly used as packing material in noses and will conform to the shapes of the nasal cavity when wet. Alternatively, a hydrophilic coating may also be applied to the outer surface of the balloon to prevent beading on the outside.
(151) Advantages of this apparatus and method include rapid circulation of the cooling fluid, rapid transfer of heat from the flexible balloon to the membranes of the nasal cavity, and flexibility in choice of coolant because the fluid is contained. Heat is transferred through the mucosa from the pool of blood in the cavernous sinus to the cooling fluid in the flexible balloon, thereby cooling the pool of blood in the cavernous sinus. Consequently, the blood in the carotid arteries, which runs through the cavernous sinus, is also cooled as it travels to the brain. In particular, the maximal heat exchange will likely be with the ascending carotid arteries immediately before entry into the intracranial space and the terminal portion of the extracranial internal carotid artery.
(152) In another aspect of the invention, as seen in
(153) In another aspect of the invention, a sponge may be inserted into the nasal cavity of a patient to substantially fill the cavity. As mentioned previously, the sponge could surround the outside of a balloon to help fill the nasal cavity. The sponges may help to fill the back of the mouth and come into intimate contact with the soft palate and upper pharynx. Alternatively, the sponge could be inserted into the nasal cavity alone. The sponge could be connected to an inlet and outlet tubular member to allow for circulation of fluids within the sponge. In contrast to the balloon, the increased surface area of the sponge would allow for better contact with the interior surfaces of the nasal cavity. Additionally, the sponges could be designed with finger or hair-like extrusions to increase the surface area, thereby increasing contact with the interior surfaces of the nasal cavity. A hollow tube could be inserted through the sponge and/or balloon to facilitate breathing.
(154) Convective Cooling in Other Parts of the Body
(155) In another aspect of this invention, a modified nasogastric tube with a flexible balloon having a chamber filled with a cooling liquid may be used to cool the brain. As seen in
(156) In use, the patient is intubated and the assembly is inserted through a patient's nostril, down the back of the throat, through the esophagus, and into the stomach. The assembly is positioned such that flexible balloon 354 is located in the nasal cavity and the esophagus and flexible balloon 358 is located in the stomach. A cooling fluid can then be infused into flexible balloons 354, 358 to expand the balloons such that they substantially fill and contact the nasal cavity, esophagus, and stomach, respectively. The cooling fluid could be pumped in through nasogastric tube 354 and suctioned out of elongate tubular member 360 at a rate sufficient to induce or maintain a desired pressure in the flexible balloons 354, 358 or a desired brain temperature. The cooling fluid may then be recirculated through flexible balloons 354, 358 via nasogastric tube 356, shaft 360, and a refrigerated pump (not shown).
(157) In another aspect of this invention, a modified laryngeal mask having a flexible balloon having a chamber filled with a cooling liquid can be used to cool the brain. As seen in
(158) In use, as seen in
(159) In another aspect of this invention, a cooling pad may be used to cool the brain via the oral cavity. As seen in
(160) In use, the assembly 400 is inserted into the oral cavity through the mouth such that the flexible balloon or pad 402 covers the retromandibular area or peritonsillar region. A cooling fluid can then be infused into the chamber of flexible balloon or pad 402 to expand it to a sufficient pressure such that flexible balloon or pad 402 is substantially in contact with the retromandibular area or peritonsillar region. The cooling fluid may then be recirculated through flexible balloon 402 via lumens 404, 406, using pump 412 and cooler 410 or a refrigerated pump. The cooling fluid can also be withdrawn or suctioned out of the flexible balloon 402 at a rate sufficient to induce or maintain a desired balloon pressure or brain temperature. Cooling of the brain may be achieved through convection or heat transfer between flexible balloon or pad 402 and the extracranial carotid artery.
(161) The cooling fluid used with these inventions may include, but is not limited to, water, saline, PFC, anti-freeze solution, or a combination thereof. The temperature of the cooling fluid will preferably be below body temperature. The temperature of the cooling fluid may be between about 37° C. to about −20° C., alternatively between about 30° C. to about −20° C., alternatively between about 20° C. to about −20° C., alternatively about 0° C., alternatively about 5° C., alternatively about −5° C., alternatively between about −5° C. to about 10° C., alternatively between about −5° C. to about 5° C., alternatively between about 0° C. to about 5° C. When saline is used as the cooling fluid, the saline will preferably be about 0° C. The cooling fluid should recirculate at a fast enough rate to maintain the low temperatures within the balloon. The flow rate of the cooling liquid by be between about 5 and about 5 L/min, alternatively between about 100 and about 400 ml/min, alternatively between about 200 and about 300 ml/min, alternatively between about 150 to about 200 ml/min.
(162) Optionally, a gel may also be optionally applied to the exterior of flexible balloons before insertion into the oral cavity. The gel would preferably have good thermal conduction properties and be a better conductor than air. Additionally, the gel could also act as a lubricant to assist in the insertion. The gel may include, but is not limited to, any aqueous gel, a poloxamer-based gel, a cellulose gel (such as KY jelly), a nasal-packing jelly, or a thermal gel. Alternatively, sponges may be attached to the surface of the balloon. Sponges, such as PVA sponges, are commonly used as packing material and will conform to the shapes of the oral cavity when wet. The sponges could be designed with finger or hair-like extrusions to increase the surface area, thereby increasing contact with the interior surfaces of the oral cavity. The sponges may fill the back of the mouth and allow for maximal cooling at the soft palate and retropharynx. Alternatively, a hydrophilic coating may also be applied to the outer surface of the balloon to prevent beading on the outside. A tube may also be inserted to allow breathing.
(163) Fluid/Gas Delivery Systems
(164) In another embodiment, the invention includes a liquid and gas delivery system for the delivery of a fixed, or substantially fixed, ratio of liquid and gas. As seen in
(165) Mixing manifold 510 can be connected to catheters 540 and 545, each containing multiple delivery ports 541 and 546 for delivery of the gas and liquid mixture to, for instance, the nasal cavity. Liquid can flow from line 530 into liquid lumens 572 and 574 of catheters 540 and 545 through ports 560 and 562, respectively. Similarly, gas can flow from line 507 into lumens 542 and 547 of catheters 540 and 545 through ports in the distal ends of the respective catheters. The gas and liquid can later be mixed and delivered to the nasal cavity through the multiple ports 541 and 546 as a nebulized spray, as described above. Pressure in the nasal cavity can be measured through pressure lines 511 and 512, which are in communication with ports 565 and 566 located near the distal ends of catheters 540 and 545 through pressure lumens 576 and 578 and ports 561 and 563, respectively. Alternatively, a separate catheter could be inserted to measure the pressure in the nasal cavity (not shown). If a pressure measured in the nasal cavity in which the liquid and gas is being delivered is found to be too high, overpressure safety device 515 will stop the flow of gas, and consequently, the flow of liquid, to the nasal cavity. Additionally, the stopcock could be closed when it is desired to only deliver a gas, for instance, oxygen, rather than cool the patient.
(166) An alternative embodiment of the liquid and gas delivery system is depicted in
(167) The fluid control reservoir 968 is rated to withstand the pressure of the compressed gas, for example the fluid control reservoir may be a poly ethylene teraphalate (PET) container tested to pressures in excess of 150 psi. In addition, a burst disk or relief valve 966, set at a value exceeding the expected operating pressure, for example 60 psi, alternatively 70 psi, alternatively 80 psi, alternatively 90 psi, may be added to the fluid reservoir container as a safety means for venting gas in the event of over pressurization. When the pressurized gas flows into fluid reservoir 968, the fluid is routed though an outlet port in the reservoir that is in fluid communication with liquid channel 980 of the dual lumen tubing (not shown). The outlet port may include fluid flow controlling device 972, such as a needle type valve or a variable diameter aperture, to adjust the flow rate of fluid into liquid channel 980 of the dual lumen tubing. In addition, gas flow channel 978 of the dual lumen tubing may also include flow controlling device 970, such as a needle type valve or a variable diameter aperture, to adjust the flow rate of gas into the gas channel of the dual lumen tubing. The flow control valves 970 and 972 of the gas and liquid channels may be independently controlled by the operator to allow full flexibility in varying the gas and/or liquid flow to optimize the gas/liquid flow ratio. The gas and liquid flow control valves 970 an 972 may have fixed orifices that produce a known constant flow for the gas and the liquid, or alternatively, the flow control valves 970 and 972 may include a selector (not shown) that would allow the operator to choose one of several sets of orifices in order to provide the operator with a number of choices for the flow, for example low flow, medium flow, high flow, induction, and maintenance flow rates. Here, each set point on the selector would use a predetermined orifice for the gas flow and a matched orifice for the liquid such that the gas/liquid flow rates and ratios would be optimized for each condition. In an alternative embodiment, the flow rate generated by the fixed orifices may be further altered while maintaining the constant gas/liquid ration, by using pressure regulator to regulate the input pressure of the gas source. In addition, liquid and gas flow meters 974 and 976 may be placed in the liquid and gas flow channels to further monitor and regulate the liquid and gas flow rates. Flow meters 974 and 976 may be any standard flow technology such as turbines, paddlewheels, variable area Rota meters or mass flow meters. In addition, in-line filters (not shown) may be placed in both the gas and liquid channels to prevent particulate matter from being introduced to the patient.
(168) Although the foregoing invention has, for the purposes of clarity and understanding, been described in some detail by way of illustration and example, it will be obvious that certain changes and modifications may be practiced which will still fall within the scope of the appended claims.