Source: http://www.google.fr/patents/US8172889
Timestamp: 2017-12-18 13:09:01
Document Index: 92671156

Matched Legal Cases: ['art 304', 'art 304', 'art 304', 'art 304', 'art 304', 'art 304', 'art 304', 'art 304']

Brevet US8172889 - Method of manufacturing a heat transfer element for in vivo cooling without ... - Google Brevets
An intravascular heat transfer device is provided with a mixing-inducing surface formed by an easily manufacturable process. The device can have a plurality of elongated, articulated segments, each having a mixing-inducing exterior surface. A flexible joint connects adjacent elongated, articulated segments....http://www.google.fr/patents/US8172889?utm_source=gb-gplus-shareBrevet US8172889 - Method of manufacturing a heat transfer element for in vivo cooling without undercuts
Numéro de publication US8172889 B2
Numéro de demande US 11/974,651
Date de dépôt 15 oct. 2007
Date de priorité 4 avr. 2002
Autre référence de publication US7288109, US20040210285, US20080046045
Numéro de publication 11974651, 974651, US 8172889 B2, US 8172889B2, US-B2-8172889, US8172889 B2, US8172889B2
Inventeurs Steven Yon, Devon Sowell
Cessionnaire d'origine Innercoll Therapies, Inc.
Citations de brevets (66), Citations hors brevets (13), Classifications (10), Événements juridiques (9)
Method of manufacturing a heat transfer element for in vivo cooling without undercuts
US 8172889 B2
1. A method of making a heat transfer device, comprising:
Providing a mold in a deposition apparatus, the mold having an inside shape such that a flexible continuous substantially conductive layer may be deposited in the mold and shaped, configured, and arranged to have at least two helical grooves formed on a heat transfer segment, the two helical grooves being joined by a circumferential segment.
2. The method of claim 1, wherein the providing further comprises providing a mold that is shaped, configured, and arranged to form a layer that lacks undercuts.
3. The method of claim 1, wherein the inside shape forms at least two heat transfer segments, the helical grooves on one of the heat transfer segments having opposite helicity from the helical grooves on another of said heat transfer segments.
4. A product formed by the process of claim 3.
This application is a divisional of U.S. patent application Ser. No. 10/785,389, filed Feb. 24, 2004, entitled “Method Of Manufacturing A Heat Transfer Element For In Vivo Cooling Without Undercuts”, which is a continuation-in-part of U.S. patent application Ser. No. 10/117,733, filed Apr. 4, 2002, entitled “Method Of Manufacturing A Heat Transfer Element For In Vivo Cooling, now U.S. Pat. No. 6,702,841.
This application also claims the benefit of U.S. provisional application Ser. Nos. 60/449,816 for a “Method of Making Heat Transfer Elements”, filed Feb. 24, 2003, 60/449,809 for a “Method of Making Heat Transfer Elements”, filed Feb. 24, 2003, and 60/451,095 for a “Molded Manufacture of a Heat Transfer Element”, filed Feb. 28, 2003. All of the prior applications are incorporated by reference herein.
Implementations of the method may include one or more of the following. Either or both of a layer of an antithrombogenic material or a lubricious material may be deposited on the biocompatible coating. A protective layer may be deposited on the mandrel so as to be the innermost layer of the device, the protective layer formed of a material which does not corrode when exposed to a working fluid, such as Au. The biocompatible coating may be selected from the group consisting essentially of Au, Pt, urethane, Teflon®, other noble metals, parylene, or other similar materials or combinations thereof. The mandrel may be formed of Al, and may be formed having a shape configured and arranged such that a material formed thereon is capable of causing mixing in a fluid flowing adjacent the material. The mandrel may be formed by a technique selected from the group consisting of machining, injection molding, laser machining, hydroforming, or other similar techniques. The surface of the heat transfer device may be bombarded with nitrogen to provide a degree of thrombogenicity either in combination with or instead of an antithrombogenic coating such as heparin. In all of the above, the depositing may be performed by a technique selected from the group consisting of CVD, PVD, sputtering, MBE, electroplating, electrochemical deposition [ECD], or other similar techniques or combinations of the above. A seed layer may be deposited on the mandrel, the seed layer formed of a material which is capable of bonding to the protective layer or to the mechanical layer. The depositing a mechanical layer may include depositing a sandwich structure. The depositing a sandwich structure may include depositing a layer of a first metal, depositing a layer of a second metal, and then depositing another layer of the first metal. The first metal may be Ni and the second metal may be Cu.
Advantages of the invention are many fold. A highly conductive heat transfer element may be manufactured conveniently. The heat transfer element may retain a high degree of flexibility so as to be able to navigate tortuous vasculature. The heat transfer element has an a traumatic profile and is biocompatible.
FIG. 9 is a schematic drawing of a helical groove showing variable indices for determination of optimum construction;
FIG. 11 is a plot showing a segment of a design for a “helical” path;
In order to obtain the benefits of hypothermia described above, it is desirable to reduce the temperature of the blood flowing to the brain (or alternatively for total body cooling, to the blood flowing out of the heart) to between 30° C. and 32° C. Given that a typical brain has a blood flow rate through each carotid artery (right and left) of approximately 250-375 cubic centimeters per minute, the heat transfer element should absorb 75-175 Watts of heat when placed in one of the carotid arteries, in order to induce the desired cooling effect. It should be noted that smaller organs may have less blood flow in the supply artery and may require less heat transfer, such as 25 Watts. For total body cooling, rates of 250-300 Watts may be required.
In addition, the rounded contours of the ridges 28, 32, 36 also allow the heat transfer element 14 to maintain a relatively a traumatic profile, thereby minimizing the possibility of damage to the blood vessel wall. A heat transfer element according to the present invention may be comprised of one, two, three, or more heat transfer segments.
Referring back to FIG. 1, the heat transfer element 14 has been designed to address all of the design criteria discussed above. First, the heat transfer element 14 is flexible and is made of a highly conductive material. The flexibility is provided by a segmental distribution of bellows sections 25, 27 that provide an articulating mechanism. Bellows have a known convoluted design that provides flexibility. Second, the exterior surface area 37 has been increased through the use of helical ridges 28, 32, 36 and helical grooves 26, 30, 34. The ridges also allow the heat transfer element 14 to maintain a relatively a traumatic profile, thereby minimizing the possibility of damage to the vessel wall. Third, the heat transfer element 14 has been designed to promote turbulent kinetic energy both internally and externally. The modular or segmental design allows the direction of the invaginations to be reversed between segments. The alternating helical rotations create an alternating flow that results in mixing the blood in a manner analogous to the mixing action created by the rotor of a washing machine that switches directions back and forth. This mixing action is intended to promote high level turbulent kinetic energy to enhance the heat transfer rate. The alternating helical design also causes beneficial mixing, or turbulent kinetic energy, of the working fluid flowing internally.
The heat transfer element can absorb or provide over 75 Watts of heat to the blood stream and may absorb or provide as much as 100 Watts, 150 Watts, 170 Watts, 250 Watts, 300 Watts, or more. For example, a heat transfer element with a diameter of 4 mm and a length of approximately 10 cm using ordinary saline solution chilled so that the surface temperature of the heat transfer element is approximately 5° C. and pressurized at 2 atmospheres can absorb about 100 Watts of energy from the bloodstream. Smaller geometry heat transfer elements may be developed for use with smaller organs which provide 60 Watts, 50 Watts, 25 Watts or less of heat transfer.
The method of manufacturing a heat transfer element will now be described in more detail. The exterior structure of the heat transfer element is of a complex shape as has been described in order to induce mixing in the flow of blood around the heat transfer element, as well as to induce mixing in the flow of working fluid within the heat transfer element. As may be clear, many varieties and shapes may be employed to cause such flow. Such shapes are termed herein as “mixing-inducing shapes”. Examples of mixing-inducing shapes include: helical, alternating helical or other enantiomorphic shapes, aberration-including shapes, bump-including shapes, channel-including shapes, crenellated shapes, hook- or horn-shapes, labyrinthine shapes, and any other shapes capable of inducing mixing. Thus, the metallic element or elements or compounds forming the heat transfer element must be sufficiently ductile to assume such shapes during deposition.
It is further noted here that while the generic term “deposition” is used, this term is intended broadly to cover any process in which metals or coating may be disposed on a mandrel or other layer of a heat transfer element. For example, deposition may include: CVD, PVD, sputtering, MBE, forms of crystal or amorphic material “growth”, spray coating, electroplating, ECD, and other methods which may be employed to form a mandrel or a coating having a mixing-inducing shape. Methods such as ECD and electroplating have the benefit of having a charged workpiece—this charge may be employed to fix the workpiece to the tool.
However the mandrel is formed, it is important for the same to have a smooth surface finish and exterior texture. In this way, the resulting heat transfer element will be smooth. A smooth mandrel allows an a traumatic device to be formed around the same. A smooth mandrel also allows a smooth metallic coating (heat transfer element) to be simply deposited around the same thus ensuring uniform heat transfer, a constant thickness of biocoating, an a traumatic profile, etc.
The order of process steps required for production of an electroform may be optimized to prevent contact of electrodeposits with harmful solutions. For example, deposition of cyanide gold may require post-rinsing with an oxidizer (typically a hypochlorite). This rinse will attack any exposed nickel. A hypochlorite rinse should therefore be applied only to electroforms before removal of the aluminum mandrel to minimize nickel exposure.
Pulse plating has been demonstrated to reduce porosity by grain refinement and to reduce the requirement for additives. In addition, pulse plated deposits have demonstrated greater ductility than DC plated deposits.
For sake of argument, it is assumed here that Ni forms the basic heat transfer element. As stated above, Ni is not hemocompatible. Thus, a biocompatible layer 106 is disposed on the mechanical layer 104 as is shown in FIG. 6. The biocompatible layer may be, e.g., urethane, parylene, Teflon®, a lubricious coating, an antithrombogenic coating such as heparin, a noble metal such as Au, or combinations of the above or other similar materials.
One difficulty with the above embodiment may be that, with use of certain working fluids, such as saline, corrosion of the mechanical layer may occur. In the case of a mechanical layer 104 of Ni, saline may be especially corrosive. Thus, a protective layer 102 may be employed that is noncorrosive with respect to saline. For example, the protective layer 102 may be made of Au. A Au protective layer 102 may encounter difficulties attaching to an aluminum mandrel, and thus if necessary a layer of Cu may be deposited on the mandrel prior to deposition of the Au layer. Following the dissolution of the mandrel, the Cu layer may also be etched away. The protective layer may generally be any noble or inert metal, or may be a polymer or other protective material such as Teflon®.
FIG. 7 also shows two layers above the mechanical layer 104: a biocompatible layer 106 and a heparin/lubricious layer 108. These may also be combined to form a single biocompatible layer. Alternatively, the biocompatible layer may be a “seed” layer which enhances the connection of the heparin/lubricious layer 108 to the underlying mechanical layer 104. Such a seed layer may be, e.g., parylene. Finally, it should be noted that the heparin/lubricious layer 108 is indicated as exemplary only: either heparin or a lubricious layer may be deposited individually or in combination. For example, in certain applications, heparin may not be necessary.
Another embodiment is shown in FIG. 8. This embodiment addresses another difficulty that may occur with various metals. For example, a mechanical layer 104 that is made entirely of Ni may have too low a burst pressure, partially due to its porosity. The protective layer 102 of FIG. 7 may address some of these concerns. A better approach may be that shown in FIG. 8. In FIG. 8, the mechanical layer 104 is broken up into several layers. Two, three, or more layers may be employed. In FIG. 8, layers 104 a and 104 c are formed of a first material such as Ni. An interior layer 104 b is deposited between layers 104 a and 104 c. This layer 104 b may be formed of a second material such as Cu. This combination of layers 104 a, 104 b, and 104 c forms a mechanical “sandwich” structure. The Cu layer 104 b (the second “metal” or “layer”) may serve to close “pinholes” that may exist within the more porous Ni layers 104 a and 104 c (the first “metal” or “layer”).
Layer Number Material Thickness
102 Au (e.g., 1/10 mil
104a Ni 3½/10
104b Cu 1/10 mil
104c Ni 3½/10
106 Au 1/10 mil
108 heparin/ 7-10 microns
In some cases, the heat transfer device may be constructed using a multi-part mold, and in particular a two-part mold. The difficulty in this case may often be the removal of the device from the two-part mold, especially with respect to more convoluted features, such as helical grooves, which may often get “caught” on a section of the mold and are thus rendered unremovable. This “catching” typically occurs in the context of an undercut.
For example, referring to FIG. 21, a multi-part mold 300 is schematically shown having an interior wall 302. A part 304 is shown within the mold. These shapes are to be construed generally—the part 304 and wall 302 may well have features that are convoluted, such as ridges or grooves or both, or dimples or knobs or both, etc.
Referring now to FIG. 22, a mold 300 is shown that creates an undercut in a part 304. In particular, interior wall 302 has a section 306 that creates a feature 308 in the part or heat transfer element 304. Here, “part” is intended to refer to a heat transfer element or a heat transfer segment, depending on context. In FIG. 22, the part 304 has an undercut, in particular at section 308, because the part 304 cannot be lifted up, in the direction indicated by arrow 310, without having the feature 308 “catch” on section 306. While the part may be maneuvered in such a way to remove the same from the mold, such practices are inconvenient and do not transfer well to large scale manufacturing.
Referring now to FIG. 23, a mold 300′ is shown that creates a feature but not an undercut in a part 304′. In particular, an interior wall 302′ of mold 300′ has a section 306′ that creates a feature 308′ in the part or heat transfer element 304′. In FIG. 23, the part 304′ does not have an undercut because the part 304′ can be lifted up, in the direction indicated by arrow 310, without having the feature 308′ “catch” on section 306′.
In an embodiment of the invention, and referring to FIG. 9, a mathematical construct is employed to find a helical groove design that can be more easily and reliably removed from a multi-part groove. Using two helical grooves with initial and terminal points at 180° intervals around the circumference of a cylinder, some combination of (φ, w, δ) should allow the resulting device to be removable from a 2-part mold. In FIG. 9, the “parting” line of the mold would be the plane of the page.
For example, an ellipse may describe the intersection of a circular cylinder and a plane. If a sequence of similar ellipses, all circumscribed around the same right circular cylinder, are constructed such that they intersect at the termini of their major axes, then by traversing alternate halves of subsequent ellipses, a path along the length of the cylinder is obtained which contains co-planar points through each of which may be drawn a line normal to the axis of the cylinder. A short segment of the resulting (3-D) path is shown in FIG. 11. Projections of this path along the directions indicated as ‘X-view’ and ‘Y-view’ are shown in FIGS. 12 and 13, respectively. If the path shown in FIG. 11 represents the (bottom) vertex of a triangular groove machined into a larger circular cylinder, then a unique plane parallel to the plane of FIG. 12 and containing the axis of the cylinder may be defined which divides the cylinder into two halves. Since the groove is normal to the plane at the corresponding intersection (of groove and plane), each of the resulting halves may be consistent with the manufacture of the grooved cylinder using a 2-part mold. The region of the space (φ, w, δ) where φ is the angle of the major axes of the ellipses relative to the cylinder axis, and w and, δ are the width and depth, respectively, of the groove defined by path shown in FIG. 11, containing grooves which are compatible with a 2-part mold has not been determined. In any case, the relaxation of the constraint of a purely helical path allows construction of a more easily manufactured part which has on at least part of its surface a groove with sufficient pitch to enhance mixing and heat transfer.
As seen by the top of FIG. 20, the parting strip 222 is employed to serve as the location adjacent to which the two mold halves come together. In this way, all of the helical invaginations, formed by ridges 224 and grooves 226, may be formed without any undercut, thereby minimizing the difficulty of removing the segment from the mold. Of course, it will be seen that the “helical” grooves and ridges always subtend an angle of less than 180°, as none extends all the way around the segment. Such discontinuities may help to increase the overall amount of mixing or turbulence created. An additional advantage is that the distal 230 and proximal 228 ends may be more easily coupled to adjoining segments or joints (not shown).
A further embodiment is shown in FIG. 24. In this embodiment, a heat transfer segment 400 of a heat transfer element is shown. Heat transfer segment 400 has a “corkscrew” design, in which the helical ridge 402 and groove 404 forms a continuous ridge and groove from the proximal end 406 of the segment to the distal end 408.
A right circular cylinder 506 is shown in the global Cartesian reference frame shown in FIG. 27, and a helical path 508 is constrained to lie in the surface of the cylinder and contains the point 510 (z=0, θ=0). The helical grooves of the heat exchange element can be constructed by sweeping the vectors {right arrow over (g)} (512) and {right arrow over (g)}′ (514) (defined in FIG. 28), which satisfy the requirement
({right arrow over (g)}×{right arrow over (g)}′)×{right arrow over (t)}=0
Determination of Extinction Angle, θc
The global coordinates of a helix constrained to lie in the surface of a cylinder, as shown in FIG. 27, are given by
x = R cos θ y = R sin θ z = P 2 π θ
where P is the linear pitch of the helix (the distance along the ‘z’ axis of the cylinder traversed by 0≦θ≦2π). The tangent, normal, and bi-normal vectors at a point on the helix are given by
t → = ( - R sin θ , R cos θ , P 2 π ) n → = ( R cos θ , R sin θ , 0 ) b → = ( P 2 π R sin θ , - P 2 π R cos θ , R 2 )
({right arrow over (g)}×{right arrow over (t)})·î=0
where î is the unit vector normal to the global (y,z) plane. θc is then the position along the helix at which the dot product is satisfied. The solution to that equation is presented graphically in FIG. 30. For a given helical pitch P and groove half-angle φ, where
φ=cos−1({right arrow over (g)}·{circumflex over (n)})=cos−1({right arrow over (g)}′·{circumflex over (n)}) eq. 6
and {circumflex over (n)} is the unit vector in the helix normal direction, the above equation is evaluated in the interval 0≦θ≦π and θc is identified as the angle θ for which the triple product vanishes. The variation of extinction angle with helical pitch for a specified groove half-angle is shown in FIG. 30.
US2077453 29 mars 1934 20 avr. 1937 American Anode Inc Therapeutical appliance
US3087493 27 avr. 1960 30 avr. 1963 George W Schossow Endotracheal tube
US3612175 1 juil. 1969 12 oct. 1971 Olin Corp Corrugated metal tubing
US3777343 28 févr. 1973 11 déc. 1973 Spiral Tubing Corp Method for forming a helically corrugated concentric tubing unit
US3826304 4 nov. 1970 30 juil. 1974 Universal Oil Prod Co Advantageous configuration of tubing for internal boiling
US3905416 * 21 mai 1974 16 sept. 1975 Hammer Hieme C Method and apparatus for fabricating molded articles
US4072146 8 sept. 1976 7 févr. 1978 Howes Randolph M Venous catheter device
US4111209 18 avr. 1977 5 sept. 1978 Datascope Corporation Topical hypothermia apparatus and method for treating the human body and the like
US4497890 8 avr. 1983 5 févr. 1985 Motorola, Inc. Process for improving adhesion of resist to gold
US4781799 8 déc. 1986 1 nov. 1988 Xerox Corporation Electroforming apparatus and process
US4863442 14 août 1987 5 sept. 1989 C. R. Bard, Inc. Soft tip catheter
US4973493 15 oct. 1987 27 nov. 1990 Bio-Metric Systems, Inc. Method of improving the biocompatibility of solid surfaces
US5112438 29 nov. 1990 12 mai 1992 Hughes Aircraft Company Photolithographic method for making helices for traveling wave tubes and other cylindrical objects
US5365750 18 déc. 1992 22 nov. 1994 California Aquarium Supply Remote refrigerative probe
US5410808 24 févr. 1993 2 mai 1995 G.P. Industries, Inc. Method of making a double wall twist tube
US5861021 20 déc. 1996 19 janv. 1999 Urologix Inc Microwave thermal therapy of cardiac tissue
US5873835 13 sept. 1995 23 févr. 1999 Scimed Life Systems, Inc. Intravascular pressure and flow sensor
US5957963 24 mars 1998 28 sept. 1999 Del Mar Medical Technologies, Inc. Selective organ hypothermia method and apparatus
US6113626 23 avr. 1998 5 sept. 2000 The Board Of Regents Of The University Of Texas System Heat transfer blanket for controlling a patient's temperature
US6146814 24 déc. 1997 14 nov. 2000 Millet; Marcus J. Methods of making composite catheters
US6149673 7 août 1998 21 nov. 2000 Radiant Medical, Inc. Method for controlling a patient's body temperature by in situ blood temperature modification
US6165207 27 mai 1999 26 déc. 2000 Alsius Corporation Method of selectively shaping hollow fibers of heat exchange catheter
US6287326 2 août 1999 11 sept. 2001 Alsius Corporation Catheter with coiled multi-lumen heat transfer extension
US6436071 8 juin 1999 20 août 2002 The Trustees Of Columbia University In The City Of New York Intravascular systems for corporeal cooling
US6520933 3 nov. 2000 18 févr. 2003 Alsius Corporation Central venous line cooling catheter having a spiral-shaped heat exchange member
US20020007203 12 juil. 2001 17 janv. 2002 Innercool Therapies, Inc. Method of manufacturing a heat transfer element for in vivo cooling
US20020016621 25 juil. 2001 7 févr. 2002 Innercool Therapies, Inc. Lumen design for catheter
US20020068964 22 janv. 2002 6 juin 2002 Innercool Therapies, Inc. Heat pipe nerve cooler
US20020072759 15 août 2001 13 juin 2002 Fry William R. Low-profile, shape-memory surgical occluder
US20020183815 4 avr. 2002 5 déc. 2002 Nest Mark Van Method of manufacturing a heat transfer element for in vivo cooling
US20030014094 13 juil. 2001 16 janv. 2003 Radiant Medical, Inc. Catheter system with on-board temperature probe
US20030040782 25 juil. 2002 27 févr. 2003 Walker Blair D. Heat exchange catheter having a helically wrapped heat exchanger
USRE31873 19 janv. 1983 30 avr. 1985 Venous catheter device
WO1999048449A1 23 mars 1999 30 sept. 1999 Innercool Therapies, Inc. Selective organ cooling apparatus and method
WO1999066970A1 15 juin 1999 29 déc. 1999 Innercool Therapies, Inc. Selective organ cooling apparatus and method
WO2001008580A1 1 août 2000 8 févr. 2001 Alsius Corporation Catheter with coiled multi-lumen heat transfer extension
WO2001013782A1 24 août 2000 1 mars 2001 Cryogen, Inc. Stretchable cryoprobe sheath
WO2001013809A1 31 juil. 2000 1 mars 2001 Radiant Medical, Inc. Heat exchange catheter with discrete heat exchange elements
WO2001013837A1 28 juil. 2000 1 mars 2001 Innercool Therapies, Inc. Method of manufacturing a heat transfer element for in vivo cooling
1 Behmann, F.W., et al.; << Heat Generation Control during Artificial Hypothermia: I: Experimental Examination of the Influence of Anesthetic Depth; Pflügers Archiv, Bd. 266, S. 408-421 (1958) (German article with English translation).
2 Behmann, F.W., et al.; Intravascular Cooling, a Method to Achieve Controllable Hypothermia; Pflügers Archive, vol. 263, pp. 145-165 (1956) (German article with English translation).
3 Behmann, F.W.; "Heat Generation Control during Artificial Hypothermia, an article about the economic problem of trembling stages"; Pflügers Archive, vol. 263, pp. 166-187 (1956) (German article with English translation).
4 Behmann, F.W.; "Regulation of heat production in experimental hypothermia of homothermal animals"; Naunyn Schmiedebergs Arch Exp Pathol Pharmakol; 228 (1-2): 126-128 (1956). (German article with English translation).
5 Behmann, F.W; "Heat Generation Control during Artificial Hypothermia: II. Theoretical Examinations"; Pflügers Archiv, Bd. 266, S. 422-446 (1958) (German article with English translation).
6 De Witte, Jan L., et al.; "Tramadol Reduces the Sweating, Vasoconstriction, and Shivering Thresholds"; Anesth Analg; vol. 87; pp. 173-179 (1998).
7 Hederer, G., et al.; "Animal Experiment Observations Regarding Cardiac Surgery under Intravascular Hypothermia"; Labgebbecjs Arch. U. Dtsch. A. Chir., Bd. 283, S. 601-625 (1957) (German article with English translation).
8 Jackson, Donald, et al; "Hypothermia : IV. Study of Hypothermia Induction Time with Various Pharmacological Agents (24617)"; Proc Soc Exp Biol Med.; 100(2): 332-335 (Feb. 1959).
9 Mokhtarani, Masoud, et al.; Buspirone and Meperidine Synergistically Reduce the Shivering Threshold; Anesth Analg; vol. 93; pp. 1233-1239 (2001).
10 Piper, S.N., et al.; "Nefopam and Clonidine in the Prevention of Postanaesthetic Shivering"; Anaesthesia; vol. 54; pp. 695-699 (1999).
11 Sharkey, A., et al., "Inhibition of Postanesthetic Shivering with Radiant Heat", 1987.
12 Wheelahan, Jennifer M., et al.; "Epidural Fentanyl Reduces the Shivering Threshold During Epidural Lidocaine Anesthesia"; Anesth Analg; vol. 87; pp. 587-590 (1998).
13 Zweifler et al, "Thermoregulatory vasoconstriction and shivering impede therapeutic hypothermia in acute ischemic stroke patients", 1996.
Classification aux États-Unis 607/105, 607/106, 607/104
Classification coopérative A61F7/12, A61F2007/0056, A61F2007/0054, A61F2007/126, A61F2007/0247
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