US20020192111A1 - Apparatus for the preparation and delivery of gas-enriched fluids - Google Patents

Apparatus for the preparation and delivery of gas-enriched fluids Download PDF

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US20020192111A1
US20020192111A1 US10/213,650 US21365002A US2002192111A1 US 20020192111 A1 US20020192111 A1 US 20020192111A1 US 21365002 A US21365002 A US 21365002A US 2002192111 A1 US2002192111 A1 US 2002192111A1
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fluid
blood
lumen
catheter
oxygen
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US10/213,650
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Vincent Divino
Seth Foerster
James Gessert
Robert Mest
Paul Zalesky
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3621Extra-corporeal blood circuits
    • A61M1/3626Gas bubble detectors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3601Extra-corporeal circuits in which the blood fluid passes more than once through the treatment unit
    • A61M1/3603Extra-corporeal circuits in which the blood fluid passes more than once through the treatment unit in the same direction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3607Regulation parameters
    • A61M1/3609Physical characteristics of the blood, e.g. haematocrit, urea
    • A61M1/361Physical characteristics of the blood, e.g. haematocrit, urea before treatment
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3607Regulation parameters
    • A61M1/3609Physical characteristics of the blood, e.g. haematocrit, urea
    • A61M1/3612Physical characteristics of the blood, e.g. haematocrit, urea after treatment
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3613Reperfusion, e.g. of the coronary vessels, e.g. retroperfusion
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3621Extra-corporeal blood circuits
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/0021Catheters; Hollow probes characterised by the form of the tubing
    • A61M25/0023Catheters; Hollow probes characterised by the form of the tubing by the form of the lumen, e.g. cross-section, variable diameter
    • A61M25/0026Multi-lumen catheters with stationary elements
    • A61M25/0028Multi-lumen catheters with stationary elements characterized by features relating to at least one lumen located at the proximal part of the catheter, e.g. alterations in lumen shape or valves
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/0021Catheters; Hollow probes characterised by the form of the tubing
    • A61M25/0023Catheters; Hollow probes characterised by the form of the tubing by the form of the lumen, e.g. cross-section, variable diameter
    • A61M25/0026Multi-lumen catheters with stationary elements
    • A61M2025/0034Multi-lumen catheters with stationary elements characterized by elements which are assembled, connected or fused, e.g. splittable tubes, outer sheaths creating lumina or separate cores
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/0021Catheters; Hollow probes characterised by the form of the tubing
    • A61M25/0023Catheters; Hollow probes characterised by the form of the tubing by the form of the lumen, e.g. cross-section, variable diameter
    • A61M25/0026Multi-lumen catheters with stationary elements
    • A61M2025/0036Multi-lumen catheters with stationary elements with more than four lumina
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00Special media to be introduced, removed or treated
    • A61M2202/04Liquids
    • A61M2202/0468Liquids non-physiological
    • A61M2202/0476Oxygenated solutions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/0021Catheters; Hollow probes characterised by the form of the tubing
    • A61M25/0023Catheters; Hollow probes characterised by the form of the tubing by the form of the lumen, e.g. cross-section, variable diameter
    • A61M25/0026Multi-lumen catheters with stationary elements
    • A61M25/0032Multi-lumen catheters with stationary elements characterized by at least one unconventionally shaped lumen, e.g. polygons, ellipsoids, wedges or shapes comprising concave and convex parts
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S128/00Surgery
    • Y10S128/03Heart-lung
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S261/00Gas and liquid contact apparatus
    • Y10S261/28Blood oxygenators

Definitions

  • the present invention relates generally to an apparatus and method for the preparation and delivery of gas-enriched fluids to gas-depleted locations, and more particularly, to a system and method for the preparation and delivery of physiologic solutions for treating conditions such as tissue ischemia and post-ischemic tissues, including, inter alia, a catheter for delivering oxygen-enriched blood to specific locations within a patient's body.
  • Cell damage may result from oxygen deprivation for even brief periods of time, which may lead to organ dysfunction or failure.
  • organ dysfunction or failure For example, heart attack and stroke victims experience blood flow obstructions or diversions that prevent oxygen from being delivered to the cells of vital tissues. Without oxygen, the heart and brain progressively deteriorate. In severe cases death results from complete organ failure. Less severe cases typically involve costly hospitalization, specialized treatments and lengthy rehabilitation.
  • Blood oxygen levels may be described in terms of the partial pressure of the oxygen dissolved in the blood (pO 2 ).
  • normal blood oxygen levels i.e., normoxia or normoxemia
  • Hypoxemic blood i.e., hypoxemia
  • hyperoxic blood i.e., hyperoxemia or hyperoxia
  • Ischemic Myocardium Circulation . Vol. 85, No.
  • Hyperbaric blood is arterial blood with a pO 2 greater than 760 mm Hg.
  • Venous blood typically has a pO 2 level less than 90 mm Hg.
  • normal venous blood oxygen levels range generally from 40 mm Hg to 70 mm Hg.
  • Blood oxygen levels also might be described in terms of hemoglobin saturation levels.
  • hemoglobin saturation is about 97% and varies only slightly as pO 2 levels increase.
  • hemoglobin saturation is about 75%.
  • Treatment of acute myocardial infarction or myocardial ischemia often comprises performing angioplasty or stenting of the vessels to compress, ablate or otherwise treat the occlusion(s) within the vessel walls.
  • angioplasty increases the size of the vessel opening to allow increased blood flow.
  • angioplasty procedures are not an attractive option for the treatment of vessel blockages.
  • Such patients typically are at increased risk of ischemia for reasons such as, poor left ventricular function, lesion type and location, or the amount of the myocardium at risk.
  • the treatment options for such patients thus include more invasive procedures such as coronary bypass surgery.
  • tissue injury typically associated with treatments of acute myocardial infarction and myocardial ischemia
  • Tissue injury is minimized or prevented by the diffusion of the dissolved oxygen from the blood or fluids to the tissue and/or blood perfusion that removes metabolites and that provides other chemical nutrients.
  • the desired treatment of acute myocardial infarction and myocardial ischemia includes perfusion of oxygenated blood or oxygen-enriched fluids.
  • tolerated balloon inflation time may be increased by the concurrent introduction of oxygenated blood into the patient's coronary artery.
  • Increased blood oxygen levels also may cause the normally perfused left ventricular cardiac tissue into hypercontractility to further increase blood flow through the treated coronary vessels.
  • the infusion of oxygenated blood or oxygen-enriched fluids also may be continued following the completion of PTCA treatment or other procedures (e.g. surgery) wherein cardiac tissue “stunning” with associated function compromise has occurred.
  • continued infusion may accelerate the reversal of ischemia and facilitate recovery of myocardial function.
  • Conventional oxygenator systems also typically have a large priming volume, i.e., the total volume of blood contained within the oxygenator, tubing and other system components, and associated devices. It is not uncommon in a typical adult patient case for the oxygenation system to hold more than one to two liters of blood. Such large priming volumes are undesirable for many reasons. For example, in some cases a blood transfusion may be necessary to compensate for the blood temporarily lost to the oxygenation system because of its large priming volume. Heaters often must be used to maintain the temperature of the blood at an acceptable level as it travels through the extracorporeal circuit. Further, conventional oxygenator systems are relatively difficult to turn on and off. For instance, if the oxygenator is turned off, large stagnant pools of blood in the oxygenator might coagulate.
  • extracorporeal circuits including conventional blood oxygenators there is a relatively high risk of inflammatory cell reaction and blood coagulation due to the relatively slow blood flow rates and the large blood contact surface area.
  • a blood contact surface area of about 1-2 m 2 and velocity flows of about 3 cm/s are not uncommon with conventional oxygenator systems.
  • relatively aggressive anti-coagulation therapy such as heparinization, is usually required as an adjunct to using the oxygenator.
  • the present invention may address one or more of the problems set forth above. Certain possible aspects of the present invention are set forth below as examples. It should be understood that these aspects are presented merely to provide the reader with a brief summary of certain forms the invention might take and that these aspects are not intended to limit the scope of the invention. Indeed, the invention may encompass a variety of aspects that may not be set forth below.
  • a system for the preparation and delivery of a gas-enriched fluid is provided.
  • the system may be used for the preparation and delivery of an oxygen-enriched fluid including blood to a specific location within a patient's body.
  • the system may include a circuit for oxygenating or enriching blood, e.g., increasing the level of dissolved oxygen in the blood.
  • the system includes an apparatus that combines a gas-supersaturated fluid with blood to form a gas-enriched fluid, advantageously for regional or localized delivery.
  • the gas-supersaturated fluid may include an oxygen-supersaturated physiologic liquid, and the blood to be enriched is blood withdrawn from the patient.
  • the system provided further includes assemblies for supplying controlled flows or supplies of the gas-supersaturated fluid and the blood.
  • the system includes an elongated, generally tubular assembly including a central lumen and at least one end placeable within a patient body proximate a tissue site to be treated, the end including an outlet port for the gas-enriched fluid.
  • the system may include a catheter defining a fluid pathway, including a proximal portion adapted for coupling to supplies of gas-supersaturated fluid and blood, and a distal portion defining a fluid pathway removably insertable within a patient's body, for infusing the gas-enriched fluid to predetermined sites.
  • the proximal portion of the catheter is adapted for coupling to a supply of gas-supersaturated fluid, and includes a pump loop through which blood drawn from a blood inlet flows.
  • the blood inlet comprises a porous side segment or axial sleeve defining the entry into an annular conduit that transitions into a lumen in fluid communication with the pump loop.
  • the inlet is disposed along the portion of the catheter removably insertable within the patient's body.
  • the blood inlet Upon insertion of the catheter through an access or opening, e.g., an introducer sheath, and upon its placement within the patient body, e.g., tip placement in or proximate the coronary ostium, the blood inlet is distal to the access sheath so as to permit blood from the patient to pass through and along the fluid path defined by the blood inlet, annular conduit, lumen and pump loop before combining with the gas-supersaturated fluid to form the gas-enriched fluid delivered to the patient via the catheter central lumen and outlet port.
  • an access or opening e.g., an introducer sheath
  • the blood inlet Upon insertion of the catheter through an access or opening, e.g., an introducer sheath, and upon its placement within the patient body, e.g., tip placement in or proximate the coronary ostium, the blood inlet is distal to the access sheath so as to permit blood from the patient to pass through and along the fluid path defined by the blood inlet,
  • a method for the preparation and delivery of a gas-enriched fluid.
  • the method may include the step of combining a gas-supersaturated fluid with blood to form a gas-enriched fluid.
  • the gas-supersaturated fluid comprises an oxygen-supersaturated physiologic liquid in which oxygen is dissolved at concentrations normalized to standard temperature and pressure (STP) that equal or exceed the volume of the solvent.
  • STP standard temperature and pressure
  • solvents which may be used include saline, lactated Ringer's, and other water-based physiologic solutions.
  • a method for delivering an oxygen-enriched fluid to a specific site within a patient's body.
  • the method comprises raising the pO 2 level of the fluid to be supplied to the patient.
  • the method may include the step of controlling or providing controlled amounts of the blood and oxygen-supersaturated fluid that are combined so as to produce an oxygen-enriched fluid for delivery to a specific predetermined site.
  • Blood pO 2 levels may be maintained, adjusted, or otherwise controlled by controlling the flow rates or by providing controlled amounts of the blood and/or oxygen-supersaturated fluid.
  • a blood-gas control method is provided.
  • the blood contact surfaces are exposed to or coated with blood proteins for some brief time interval, usually at least several minutes, before the start of infusion of oxygen-supersaturated fluid.
  • fluid contact surfaces are exposed to or pre-wetted with liquids, e.g., saline, ethanol and benzalkonium heparin, before use.
  • the fluid contact surfaces also do not include any substance which promotes such bubble formation, e.g., hydrophobic surfaces that are difficult to wet, teflon, teflon-composite liners, silicone oils, etc. Hydrophillic fluid contact surfaces are typically useful.
  • the embodiments may be used in conjunction with angiographic or guiding catheters, arterial sheaths, and/or other devices used in angioplasty and in other interventional cardiovascular procedures.
  • the system may be used in applications involving one or more vascular openings, i.e., in either contralateral or ipsilateral procedures.
  • the catheter may include proximal and distal ends and a central lumen. The proximal end is adapted for the catheter to receive a supply of the gas-supersaturated fluid and to receive the blood.
  • the distal end is removably insertable within a patient's body through a second location such as the patient's right femoral artery.
  • the distal end includes at least one port in fluid communication with the central lumen and through which the gas-enriched fluid may exit.
  • the distal portion of the catheter may be adapted with a tip portion shaped so as to promote insertion of the device, such as through the same sheath used for interventional procedures like angioplasty, to specific predetermined locations within a patient's body. Examples of tip portion shapes which may be used include any of the standard clinically accepted tip configurations used with devices like guide catheters for providing access to and for holding in locations like the coronary ostium.
  • the method may further include the step of positioning the portion of the distal end of the catheter including the fluid exit port at a predetermined location within a patient body proximate to the tissue to be treated.
  • the system may be used along with one or more of any of a number of suitable, standard-size, clinically accepted guide catheters and/or introducer sheaths.
  • the system may comprise a catheter, a catheter and guide catheter, or a catheter and sheath, for use within a guide catheter or introducer sheath used for the primary interventional procedure.
  • blood is drawn between the catheter and guide catheter or sheath assemblies of the present invention, between the catheter assembly of the present invention and the guide catheter or introducer sheath used for the primary interventional procedure, or from the annular space between the guide catheter and the introducer sheath.
  • the preferred gas-supersaturated fluid for use in accordance with the present invention is an oxygen-supersaturated fluid.
  • other fluids may be used depending upon the circumstances involved in a particular desired application, such as, for example, supersaturated fluids in which one or more gases such as helium, nitrous oxide, carbon dioxide and air are dissolved.
  • the oxygen-supersaturated fluid may include a dissolved oxygen volume normalized to standard temperature and pressure of between about 0.5 and about 3 times the volume of the solvent.
  • the fluid is supplied to the system at a pressure of between about 250 p.s.i. and about 5000 p.s.i. The exact pressure may vary depending upon the circumstances involved in a particular application.
  • the oxygen-supersaturated fluid supplied may be a sterile fluid which does not include gas, surface, or bubble nucleation sites at which clinically significant bubbles may form.
  • the catheter system of the present invention is typically sized in accordance with the circumstances involved in a particular application. In general, the sizes of the various system components will be on the order of the sizes of clinically accepted interventional cardiovascular devices. Usually, the extracorporeal loop of the present invention is less than four meters in total length. Thus, for example, where the system supports blood flow rates between 100 ml/min and 175 ml/min, the priming volume would be approximately 35 ml.
  • FIG. 1 is a schematic diagram of an exemplary embodiment of a catheter system used in a contralateral interventional procedure in accordance with the present invention.
  • FIG. 2 is a cross-sectional view of part of an exemplary embodiment of a catheter system including an angled blood flow path in accordance with the present invention.
  • FIG. 3 is a cross-sectional view of part of an alternate exemplary embodiment of a catheter system including an angled blood flow path in accordance with the present invention.
  • FIG. 4 is a cross-sectional view of part of another exemplary embodiment of a catheter system including a straight blood flow path in accordance with the present invention.
  • FIG. 4A is a cross-sectional view along line A-A in FIG. 4 of the exemplary embodiment of a catheter system including a straight blood flow path shown in accordance with the present invention.
  • FIG. 5 is a perspective view of part of an exemplary embodiment of a catheter system including an exemplary oxygen-supersaturated fluid outlet in accordance with the present invention.
  • FIG. 5A is a cross-sectional view along line A-A in FIG. 5 of the part of the exemplary embodiment of a catheter system including an exemplary oxygen-supersaturated fluid outlet shown in accordance with the present invention.
  • FIG. 5B is a view of the exemplary oxygen-supersaturated fluid outlet shown in FIG. 5 in accordance with the present invention.
  • FIG. 6 is a cross-sectional view of part of an exemplary embodiment of a catheter system including an integrated blood inlet introducer sheath in accordance with the present invention.
  • FIG. 7 is a schematic diagram of an exemplary embodiment of a catheter system for use in an ipsilateral interventional procedure in accordance with the present invention.
  • FIG. 8 is a cross-sectional view of part of an exemplary guide catheter including a liner used with an exemplary embodiment of a catheter system in accordance with the present invention.
  • FIG. 8A is a cross-sectional view of the exemplary guide catheter shown in FIG. 8, without the liner, in accordance with the present invention.
  • FIG. 9 is a cross-sectional view of part of an exemplary catheter system including an integral blood draw comprising a porous side blood inlet in accordance with the present invention.
  • FIG. 10 is a cross-sectional view of part of an exemplary catheter system including an integral blood draw comprising an axial blood inlet in accordance with the present invention.
  • FIG. 10A is a cross-sectional view along line A-A in FIG. 10 of the part of an exemplary catheter system shown in accordance with the present invention.
  • FIG. 11 is a view of part of an alternate exemplary catheter system including an integral blood draw comprising a porous side blood inlet in accordance with the present invention.
  • FIG. 11A is a cross-sectional view along line A-A in FIG. 11 of part of an alternate exemplary catheter system including an integral blood draw comprising a porous side blood inlet in accordance with the present invention.
  • FIG. 11B is a cross-sectional view along line B-B in FIG. 11 of part of an alternate exemplary catheter system including an integral blood draw comprising a porous side blood inlet in accordance with the present invention.
  • FIG. 11C is a cross-sectional view along line C-C in FIG. 11 of part of an alternate exemplary catheter system including an integral blood draw comprising a porous side blood inlet in accordance with the present invention.
  • FIG. 11D is a cross-sectional view along line D-D in FIG. 11 of part of an alternate exemplary catheter system including an integral blood draw comprising a porous side blood inlet in accordance with the present invention.
  • FIG. 12 is a cross-sectional view of an exemplary tip configuration of a catheter in accordance with the present invention.
  • FIG. 12A is a cross-sectional view along line A-A in FIG. 12 of an exemplary tip configuration of a catheter in accordance with the present invention.
  • FIG. 12B is a cross-sectional view along line B-B in FIG. 12 of an exemplary tip configuration of a catheter in accordance with the present invention.
  • FIG. 13 is a cross-sectional view of an alternate exemplary tip configuration of a catheter in accordance with the present invention.
  • FIG. 13A is a cross-sectional view along line A-A in FIG. 13 of an alternate exemplary tip configuration of a catheter in accordance with the present invention.
  • FIG. 13B is a cross-sectional view along line B-B in FIG. 13 of an alternate exemplary tip configuration of a catheter in accordance with the present invention.
  • FIG. 14 is a cross-sectional view of an alternate exemplary tip configuration of a catheter in accordance with the present invention.
  • FIG. 14A is a cross-sectional view of a further alternate exemplary tip configuration of a catheter in accordance with the present invention.
  • FIG. 15 is an isometric view of an exemplary bubble detector transducer in accordance with the present invention.
  • FIG. 15A is a partially exploded view of a portion of the bubble detector transducer shown in FIG. 15
  • the various embodiments are described herein in the context of interventional cardiovascular applications generally involving acute or transient ischemia or post-ischemic tissues.
  • the present invention may also useful in other medical applications, such as cancer therapy (e.g., the delivery of oxygen-enriched fluids directly into poorly vascularized tumors during radiation or chemotherapy treatments), neurovascular applications (e.g., the treatment of stroke and cerebral trauma patients), lung support in trauma and lung disease patients, and wound care management.
  • the present invention may be used to raise oxygen levels, for example, in venous and arterial blood, in blood substitutes, e.g., perfluorocarbons, and in combinations thereof, for the sake of clarity and convenience reference is made herein only to arterial blood.
  • blood substitutes e.g., perfluorocarbons, and in combinations thereof
  • the present invention also may be used in connection with drug fluid infusion therapies.
  • drug fluids used in cardiovascular and neurological procedures which may be infused in accordance with the present invention include, without limitation, vasodilators (e.g., nitroglycerin and nitroprusside), platelet-actives (e.g., ReoPro and Orbofiban), thrombolytics (e.g., t-PA, streptokinase, and urokinase), antiarrhythmics (e.g., lidocaine, procainamide), beta blockers (e.g., esmolol, inderal), calcium channel blockers (e.g., diltiazem, verapamil), magnesium, inotropic agents (e.g., epinephrine, dopamine), perofluorocarbons (e.g., fluosol), crystalloids (e.g., normal saline, lactated ring
  • FIG. 1 a system is provided in which blood is combined with an oxygen-supersaturated fluid to form an oxygen-enriched fluid that may be delivered to a particular predetermined area within a patient's body for the treatment of conditions such as tissue ischemia and post-ischemic tissues.
  • a system 10 includes a blood draw 12 comprising a continuous fluid flow path between a vascular access site 14 of a patient body and a pump 16 .
  • the selection of the vascular access site typically is made by a physician or caregiver and depends upon the circumstances surrounding the particular application involved.
  • the particular vascular access site illustrated in FIG. 1 is the left femoral artery.
  • the blood pump 16 may be one of the many commercially available and clinically accepted blood pumps suitable for use with human patients.
  • An example of one such pump is the Model 6501 RFL3.5 Pemco peristaltic pump available from Pemco Medical, Cleveland, Ohio.
  • the pump 16 draws blood from the patient and provides a supply of blood via line 18 to the inlet 20 of catheter 22 .
  • the flow characteristics of the blood will depend upon the circumstances surrounding the particular application involved.
  • the supply of blood to the blood inlet 20 of catheter 22 will be a controlled flow defined by the flow parameters selected by the caregiver.
  • Factors influencing the determination of blood flow characteristics may include one or more of the many clinical parameters or variables of the blood to be supplied to the catheter or of the oxygen-enriched fluid to be delivered to the patient, e.g., the size of the patient, the percentage of overall circulation to be provided, hemolysis, hemodilution, pO 2 , pulsatility, mass flow rate, volume flow rate, temperature, hemoglobin concentration and pH.
  • the system 10 may include one or more gas bubble detectors, at least one of which is capable of detecting the presence of microbubbles, i.e., bubbles with diameters of about 7 to 10 microns to about 200 microns (see, e.g., FIG. 12).
  • the system may include one or more macrobubble detectors to detect larger bubbles, such as bubbles with diameters of 1 millimeter or more.
  • macrobubble detectors may comprise any suitable commercially available detector, such as an outside, tube-mounted bubble detector including two transducers measuring attenuation of a sound pulse traveling from one side of the tube to the other.
  • One such suitable detector may be purchased from Transonic Inc. of New York.
  • the microbubble and macrobubble detectors provide the physician or caregiver with a warning of potentially clinically significant bubble generation.
  • the system 10 also may include various conventional items, such as sensors, flow meters (which may also serve a dual role as a macrobubble detector), or other clinical parameter monitoring devices; hydraulic components such as accumulators and valves for managing flow dynamics; access ports which permit withdrawal of fluids; filters or other safety devices to help ensure sterility; or other devices that generally may assist in controlling the flow of one or more of the fluids in the system 10 .
  • any such devices are positioned within the system and used so as to avoid causing the formation of clinically significant bubbles within the fluid flow paths.
  • the catheter 22 includes a proximal portion 24 and a distal portion 26 , the distal portion being removably insertable within a patient body through a vascular access or opening 36 .
  • the proximal portion 24 includes blood inlet 20 .
  • Blood inlet 20 and line 18 may be adapted for releasably coupling, e.g., with a clinically accepted fluid connection apparatus such as a Luer lock, to enable the catheter 22 to receive the blood supplied via line 18 .
  • the catheter 22 includes a lumen defining a continuous blood flow path from the blood inlet 20 to a fluid exit port proximate the distal tip 28 of catheter 22 .
  • the proximal portion 24 of catheter 22 also includes a fluid inlet port 30 adapted to couple to a supply 32 of oxygen-supersaturated fluid.
  • the port 30 is in fluid communication with the supply 32 and with line 34 .
  • Line 34 comprises one or more capillaries or other elongated generally tubular members including central lumens, either alone or in an array, each defining a continuous fluid flow path between port 30 and the blood flow path of the catheter 22 .
  • the oxygen-supersaturated fluid is usually supplied to port 30 in accordance with parameters specified and selected by the caregiver for the desired clinical indication.
  • the flow of oxygen-supersaturated fluid is generally steady and continuous, although variable or intermittent flows may be used. Flow rates may range from about 0.1 cc/min to about 40 cc/mm, although particularly advantageous flow rates may be between about 2 cc/min and 12 cc/min.
  • Oxygen concentrations may range from about 0.5 cc O 2 per cc physiologic solution to about 3 cc O 2 per cc physiologic solution, although particularly advantageous concentrations may be about 1 cc O 2 per cc physiologic solution.
  • the oxygen-supersaturated fluid is provided at a temperature such that when the fluid combines with blood to form the oxygen-enriched fluid to be infused, the oxygen-enriched fluid is about 37° C., i.e., system operation does not significantly affect patient blood temperature.
  • FIG. 2 shows an embodiment in which catheter portion 40 comprises a section of the catheter in which the flows of blood and oxygen-supersaturated fluid combine.
  • Catheter portion 40 comprises the proximal end of an elongated tubular member 48 , including a generally centrally disposed fluid return lumen 52 , disposed within a housing 42 including a blood inlet lumen 44 .
  • Lumen 44 defines a continuous fluid flow path between catheter blood inlet port 46 and the proximal end 50 of fluid return lumen 52 .
  • the distal portion of member 48 (not shown) is removably insertable within a patient body and includes the exit port through which fluid traveling within fluid return lumen 52 is delivered to a site within a patient's body.
  • Housing 42 typically comprises a biocompatable, molded polymeric material.
  • the exact size and shape of housing 42 may vary depending upon the circumstances involved in a particular application.
  • FIG. 2, by way of example, shows a generally y-shaped configuration.
  • the tubular member 48 may be integrally formed with housing 42 .
  • tubular member 48 may comprise clinically approved polymeric tubing.
  • the proximal end of member 48 is fixedly attached within housing 42 .
  • the joining of housing 42 and member 48 is accomplished by solvent or adhesive bonding or insert or over molding.
  • lumen 44 also may vary depending upon the circumstances involved in a particular application.
  • FIG. 2 shows a lumen 44 defining an angled blood flow path.
  • a straight or curved blood flow path might also be used. See, e.g., FIG. 4.
  • any difference between the inner diameter of the proximal end of member 48 and the diameter of lumen 44 at the proximal end 50 of fluid return lumen 52 is minimized or eliminated to promote smooth blood flow.
  • Catheter portion 40 also includes the distal portion of an oxygen-supersaturated fluid delivery line 54 .
  • the line 54 comprises at least one elongated generally tubular member including a central lumen defining a fluid flow path between a fluid inlet port (not shown in FIG. 2) disposed at the proximal end of line 54 and fluid exit port 56 disposed at the distal end 58 of line 54 .
  • Catheter portion 40 also may include one or more stress/strain relief assemblies 60 , 62 .
  • the proximal end of line 54 may be adapted to releasably couple to a supply of oxygen-supersaturated fluid.
  • the fluid exit port 56 may be disposed within the flow path defined by fluid return lumen 52 .
  • a continuous fluid flow path is defined between the supply of oxygen-supersaturated fluid and a predetermined site within a patient's body proximate the distal end of fluid return lumen 52 .
  • the portions proximate to fluid exit port 56 of fluid return lumen 52 and of the distal end 58 of line 54 are generally straight, and their longitudinal axes approximately coincide, so that any difference in the direction of blood flow in lumen 52 proximate port 56 and the direction of exit fluid flow through port 56 is minimized or eliminated.
  • fluid exit port 56 may be sufficiently downstream of the proximal end 50 of fluid return lumen 52 that the fluid exiting port 56 avoids any fluid flow disruption or non-laminar flow associated with the boundary between housing 42 and member 48 that might cause the formation of clinically significant gas bubbles.
  • the exit port for the oxygen-supersaturated fluid may be disposed upstream of the proximal end of the fluid return lumen. See, e.g., FIGS. 3 and 4.
  • an oxygen-supersaturated fluid line 64 may include a distal portion 66 including a fluid exit port 68 at the outer boundary of lumen 44 .
  • the longitudinal axis of line 64 proximate port 68 and the longitudinal axis of the portion of lumen 44 downstream of port 68 advantageously coincide, while the longitudinal axis of line 64 proximate port 68 and the longitudinal axis of the portion of lumen 44 upstream of port 68 advantageously form an angle 70 comprising an acute angle which permits the smooth introduction of fluid from line 64 into the blood flow through lumen 44 .
  • the angle 70 may be about thirty degrees, for instance.
  • the portion of line 54 extending from housing 42 into the blood flow path may be rigid enough to comprise a cantilever-like member.
  • the extending portion of the oxygen-supersaturated fluid flow line 76 also may comprise a more flexible member which tends to align itself naturally within blood flow lumen 74 along the path of least resistance.
  • the distal end of line 76 may be supported in place or otherwise oriented within the lumen 74 by one or more wings 72 extending between the distal end of oxygen-supersaturated line 76 and the outer wall or boundary defining lumen 74 .
  • the flexibility and positioning of the lines 54 and 76 depend upon the circumstances involved in a particular application, e.g., the material hardness, line profile, the number of capillaries making up the line, and the desired fluid exit location.
  • the oxygen-supersaturated fluid is injected so as to minimize or avoid altogether blood cell damage.
  • An exemplary oxygen-supersaturated fluid outlet is shown in FIG. 5.
  • the oxygen-supersaturated fluid line 80 is disposed within fluid delivery lumen 84 .
  • the distal tip of line 80 is oriented within lumen 84 by one or more ribs or spacers 82 securing the distal portion of line 80 .
  • the line 80 includes one or more capillaries 86 (see FIG. 5B) each including a central lumen 88 through which oxygen-supersaturated fluid flows.
  • FIG. 5B shows a line 80 comprising four capillaries 86 and including a distal tip of generally conical shape.
  • the ends of each capillary 86 may form an included angle 90 of about 52 degrees, for instance.
  • the capillaries may be made of glass sheathed in polyimide, with ground and polished distal ends to help minimize or eliminate the formation of clinically significant bubbles and fluid flow disruptions.
  • the line 80 may include four 100 micron inner diameter by 350 micron outer diameter tubes, for instance, potted together with epoxy at their proximal and distal ends.
  • the inner diameter may be in the range of about 20 to about 1000 microns, with an inner diameter of about 100 to about 125 microns being particularly advantageous.
  • the exact size and shape of the distal end and tip of line 80 may vary depending upon the circumstances involved in a particular application. Examples of possible configurations include, without limitation, flat, blunt, squared, pencil-shaped, curved, parabolic, hyperbolic, and pyramidal.
  • the catheter includes an oxygen-enriched fluid return line 100 and a blood draw assembly comprising a sheath 102 and housing 104 .
  • the housing 104 includes a lumen 106 which forms a blood flow path between the lumens of sheath 102 and tube 108 .
  • Tube 108 comprises the line which supplies blood to the blood pump (not shown in FIG. 6) of the system.
  • the line 100 is generally centrally disposed through the housing 104 and within the central lumen of the sheath 102 .
  • the sheath 102 Upon insertion of the distal portion of line 100 into a patient's body, the sheath 102 is positioned within a vascular access sheath, guide catheter, or other such access device, so that blood from the patient may enter the annular space 110 between the outer wall of line 100 and the inner wall of sheath 102 .
  • the proximal end of line 100 may include a stress/strain relief assembly 112 .
  • FIG. 7 is a schematic diagram illustrating a use of the catheter system with a separate arterial access sheath 114 .
  • the sheath 114 may be one of the many sizes and types of clinically accepted arterial access sheaths suitable for use in interventional cardiovascular procedures.
  • the proximal end 116 of sheath 114 is adapted with a seal or other such device which permits the insertion of catheters, guidewires, or other interventional devices through the sheath 114 and into the body without unnecessary loss of blood. Blood drawn through the lumen 118 of sheath 114 travels via line 120 to blood pump 122 before being enriched and returned to the body.
  • the blood returns via line 124 and the catheter portion 126 , where the blood flow combines with a flow of oxygen-supersaturated fluid delivered via line 128 from a supply 130 to form the oxygen-enriched fluid delivered to the patient via the distal portion 132 of the catheter system.
  • FIGS. 8 and 8A show an alternate embodiment of the catheter system.
  • a guide catheter 140 including a distal tip (not shown) removably insertable within a patient's body is placed through an outer arterial access sheath 142 .
  • the sheath 142 may be any one of the many types of clinically accepted sheaths typically used in interventional cardiovascular procedures to gain access to a patient's vasculature.
  • the guide catheter 140 includes a liner 144 .
  • the liner 144 is deformable and may be either partially (not shown) or completely (see FIG. 8A) removed.
  • lumen 146 of guide catheter 140 When a positive pressure is applied to lumen 146 of guide catheter 140 , e.g., when angiographic dyes are introduced into the lumen 146 , and when the liner 144 is in place covering the blood inlet holes 148 through the wall of guide catheter 140 , the liner 144 presses against and closes inlet holes 148 .
  • a negative pressure is applied to lumen 146 of guide catheter 140 , e.g., during the withdrawal of blood from the patient, the liner deforms as necessary to allow the entry of blood into lumen 146 through inlet holes 148 .
  • the fluid return line 150 may include a proximal portion 152 having smaller internal and external diameters than the distal portion 154 of line 150 .
  • the transition region 156 is disposed downstream of blood inlet holes 148 so as to permit the entry of blood into lumen 146 .
  • the transition region 156 comprises a section of the line 150 in which the external and internal diameters of the line 150 increase along its length.
  • the flow of blood in line 150 combines with oxygen-supersaturated fluid exiting at the end 158 of oxygen-supersaturated fluid supply tube 160 .
  • the tube 160 may comprise either a single capillary or tube, or a bundle of capillaries or tubes.
  • FIG. 9 describes part of a catheter system including an integral blood draw comprising an annular porous side blood inlet 170 .
  • the catheter 172 may be used along with a guide catheter or access sheath (not shown in FIG. 9). Blood is drawn from the patient and through the inlet 170 into catheter outer lumen 174 . From there, the blood circulates through a blood pump and is delivered back to the patient via catheter inner lumen 176 .
  • the inner lumen 176 includes a proximal portion 178 having relatively smaller internal and external diameters than distal portion 180 , and a transition region 182 joining the two portions.
  • Oxygen-supersaturated fluid supply tube 184 includes a fluid exit port 186 disposed within the distal portion 180 of catheter 172 .
  • the fluid exiting tube 184 enters the blood flow within lumen 176 downstream of any sharp pressure drops or other flow disturbances associated with the increase in the inner diameter of lumen 176 in the transition region 182 .
  • Ribs or wings 188 or another such centering device may be used to hold the distal portion of tube 184 in place.
  • the integral blood inlet of a catheter 190 comprises an axial blood inlet 192 .
  • Blood from the patient is drawn from the interior of a guide catheter or sheath, or directly from the patient's vasculature, through the inlet 192 , and into catheter outer lumen 194 . From there the blood travels through a blood pump (not shown) and is returned to the patient via inner lumen 196 .
  • the inner lumen 196 includes a proximal portion 198 having relatively smaller internal and external diameters than distal portion 200 , and a transition region 202 joining the two portions.
  • Oxygen-supersaturated fluid supply tube 204 includes a fluid exit port 206 disposed within the distal portion 200 of catheter 190 , and ribs or wings 208 may be used to hold the distal portion of tube 204 in place.
  • the proximal portion 198 of inner lumen 196 may be fixed within the interior of outer lumen 194 by a further set or ribs or wings or other similar positioning device. As shown in FIG. 10, the proximal portion 198 of lumen 196 is free to naturally follow a path of least resistance through lumen 194 .
  • the proximal portion of tube 204 likewise may be secured within lumen 196 or be free as shown.
  • FIGS. 11 and 11A-D show part of an alternate exemplary catheter system including an integral blood draw.
  • a porous side blood inlet 210 comprising a plurality of channels 212 through the outer wall of catheter 214 allows blood from the patient to enter outer lumen 216 .
  • the blood in lumen 216 passes through a blood pump (not shown in FIG. 11) before returning to the patient via lumen 218 .
  • the blood combines with an oxygen-supersaturated fluid supplied via a tube 220 .
  • the tube 220 along at least a portion of its length, may be disposed within the lumen 218 .
  • the distal tip of the tube 220 is positioned along the longitudinal axis of lumen 218 and secured in place by one or more centering fins or spacers 222 .
  • the catheter 214 also may include a lumen 224 through which blood proximate the distal tip 226 of the catheter 214 may be drawn, e.g., to provide a blood sample for use in determining blood pO 2 or in the monitoring of others clinical parameters, to ascertain blood pressure at the distal end of the catheter, etc.
  • the distal tip 226 of catheter 214 includes an ultrasonic bubble detector 228 or similar assembly for detecting the presence of clinically significant bubbles in the oxygen-enriched fluid delivered to the patient body via lumen 218 .
  • the catheter 214 may also include one or more lumens 230 within which leads coupled to the bubble detector 228 are disposed. 5
  • FIGS. 12 - 14 illustrate alternate exemplary tip configurations of a catheter.
  • FIG. 12 shows a straight tip portion 232 including a bubble detector 236 disposed proximate the tip 234 of the catheter.
  • Bubble detector leads 238 comprising one or more pairs of insulated wires or coaxial wires may be disposed as shown for example in FIG. 12A within the catheter side wall.
  • FIG. 13 illustrates a straight tip portion 240 including a dual transducer bubble detector 242 , bubble detector leads 244 , and a monorail guide lumen 246 through which a guidewire (not shown) may be thread to assist in the placement of the catheter within a patient body.
  • FIGS. 14 an 14 A illustrate alternate configurations of a catheter tip including a monorail guide lumen 248 .
  • the catheter tip as shown in the drawings may include a relatively uniform wall thickness and be of generally circular cross section (FIG. 14), or it may have a varying wall thickness and assume a more tear-drop shape (FIG. 14A).
  • a catheter tip also may include a radiopaque band 250 to aid the physician or caregiver in placing the device.
  • the band 250 comprises one or more metals or metal alloys, e.g., platinum, gold, tungsten, and iridium, and platinum-iridium and other high density materials that are visible under fluoroscopy.
  • FIGS. 15 and 15A A further exemplary bubble detector transducer 252 is shown in FIGS. 15 and 15A.
  • the transducer 252 which may be bonded or otherwise fixedly attached to or within the distal portion of the catheter, may include a single transducer operable in a pulse echo mode, i.e., it can send out an acoustic pulse and sense its reflection.
  • the transducer 252 includes an inner sleeve 254 , a layer of wrapped piezo-electric film 256 , a metal band 258 , and an outerjacket 260 .
  • the inner sleeve 254 comprises a polyimide sleeve.
  • the wrapped film 256 comprises a metallized polyvinylidenefluoride (PVDF) film including a conductive upper layer 262 , a conductive lower layer 264 , and an insulative inner layer 263 separating the upper and lower layers.
  • PVDF polyvinylidenefluoride
  • the metallized film is folded and then wrapped at least once (typically about two to five times) about the inner sleeve 254 . This folding permits the use of thinner film that exhibits higher capacitance and lower impedance than a more conventional transducer so that the wire leads 266 , which are long, thin wires, may be driven better.
  • Wire leads 266 are connected to the outermost surfaces of the layers 262 , 264 with a conductive epoxy 268 .
  • the band 258 may comprise a foil of aluminum or a band of a metal which reflects the outward acoustic pulse.
  • the band 258 comprises a radiopaque material so that the band may also act as a marker to promote placement of the device.
  • the outer jacket 260 may be made of pebax or another suitable material which provides support to the structure. It should further be understood that the bubble detector illustrated in FIGS. 15 and 15A is advantageously a compact device, e.g., air spaces between the layers of the bubble detector are minimized or eliminated. For example, any air voids may be filled with an epoxy or other suitable filler material.
  • the electronic circuitry 271 associated with the bubble detector transducer 252 causes the transducer 252 to emit ultrasonic pulses typically in the range of 20-30 MHz. In the pulse echo mode, these ultrasonic pulses are transmitted in a pulse train having a frequency of about 20-50 kHz. Thus, approximately ten reflections may be sampled from a single bubble as it passes by the transducer 252 , which is about 1 to 1.5 millimeters in length. After the pulses of ultrasonic energy are delivered during a positive portion of this duty cycle, the circuitry 271 waits approximately 0.5 microseconds to allow for a “ring down” period. Then, the reflected signals may be measured, typically for at least three bounces, before the next ultrasonic signals are transmitted.
  • the present invention has been described in terms of exemplary embodiments.
  • the operating parameters for the system may be varied, typically with a physician or caregiver specifying and selecting them for the desired clinical indication.
  • other embodiments which may be readily devised by persons of ordinary skill in the art based on the teachings set forth herein, may be within the scope of the invention which is defined by the appended claims.
  • the present invention may be modified and practiced in different but equivalent manners that will be apparent to those skilled in the art having the benefit of the teachings set forth herein.

Abstract

A gas-enriched fluid is provided by the combination of a first fluid, such as a patient's blood, with a second gas-supersaturated fluid, such as an oxygen supersaturated fluid. In this example, a catheter assembly includes a portion that receives the patient's blood from a pump and that receives the oxygen supersaturated fluid from an appropriate fluid source. The oxygen supersaturated fluid is advantageously combined with the blood in an area of laminar flow, and then this gas-enriched fluid is delivered to the patient through an appropriate lumen coupled to the portion of the catheter assembly.

Description

    RELATED APPLICATIONS
  • This application is a continuation-in-part of U.S. patent application Ser. No. 08/915,532, filed on Aug. 15, 1997, entitled “System and Method for Generalized Extracorporeal Support,” by Spears et. al, which is incorporated herein by reference.[0001]
  • FIELD OF THE INVENTION
  • The present invention relates generally to an apparatus and method for the preparation and delivery of gas-enriched fluids to gas-depleted locations, and more particularly, to a system and method for the preparation and delivery of physiologic solutions for treating conditions such as tissue ischemia and post-ischemic tissues, including, inter alia, a catheter for delivering oxygen-enriched blood to specific locations within a patient's body. [0002]
  • BACKGROUND OF THE INVENTION
  • Oxygen is a crucial nutrient for human cells. Cell damage may result from oxygen deprivation for even brief periods of time, which may lead to organ dysfunction or failure. For example, heart attack and stroke victims experience blood flow obstructions or diversions that prevent oxygen from being delivered to the cells of vital tissues. Without oxygen, the heart and brain progressively deteriorate. In severe cases death results from complete organ failure. Less severe cases typically involve costly hospitalization, specialized treatments and lengthy rehabilitation. [0003]
  • Blood oxygen levels may be described in terms of the partial pressure of the oxygen dissolved in the blood (pO[0004] 2). Typically, for arterial blood, normal blood oxygen levels (i.e., normoxia or normoxemia) range from 90-110 mm Hg. Hypoxemic blood (i.e., hypoxemia) is arterial blood with a pO2 less than 90 mm Hg. Hyperoxic blood (i.e., hyperoxemia or hyperoxia) is arterial blood with a pO2 greater than 400 mm Hg (see Cason et. al (1992), Effects of High Arterial Oxygen Tension on Function, Blood Flow Distribution, and Metabolism in Ischemic Myocardium, Circulation. Vol. 85, No. 2, pp. 828-838), but less than 760 mm Hg (see Shandling et al. (1997), Hyperbaric Oxygen and Thrombolysis in Myocardial Infarction: The “HOT MI” Pilot Study, American Heart Journal, Vol. 134, No. 3, pp. 544-550). Hyperbaric blood is arterial blood with a pO2 greater than 760 mm Hg. Venous blood typically has a pO2 level less than 90 mm Hg. In the average adult, for example, normal venous blood oxygen levels range generally from 40 mm Hg to 70 mm Hg.
  • Blood oxygen levels also might be described in terms of hemoglobin saturation levels. For normal arterial blood, hemoglobin saturation is about 97% and varies only slightly as pO[0005] 2 levels increase. For normal venous blood, hemoglobin saturation is about 75%.
  • In patients who suffer from acute myocardial infarction, if the myocardium is deprived of adequate levels of oxygenated blood for a prolonged period of time, irreversible damage to the heart can result. Where the infarction is manifested in a heart attack, the coronary arteries fail to provide adequate blood flow to the heart muscle. [0006]
  • Treatment of acute myocardial infarction or myocardial ischemia often comprises performing angioplasty or stenting of the vessels to compress, ablate or otherwise treat the occlusion(s) within the vessel walls. For example, a successful angioplasty increases the size of the vessel opening to allow increased blood flow. [0007]
  • Even with the successful treatment of occluded vessels, a risk of tissue injury may still exist. During percutaneous transluminal coronary angioplasty (PTCA), the balloon inflation time is limited by the patient's tolerance to ischemia caused by the temporary blockage of blood flow through a vessel during balloon inflation. Reperfusion injury also may result, for example, due to slow coronary reflow or no reflow following angioplasty. [0008]
  • For some patients angioplasty procedures are not an attractive option for the treatment of vessel blockages. Such patients typically are at increased risk of ischemia for reasons such as, poor left ventricular function, lesion type and location, or the amount of the myocardium at risk. The treatment options for such patients thus include more invasive procedures such as coronary bypass surgery. [0009]
  • To reduce the risk of tissue injury typically associated with treatments of acute myocardial infarction and myocardial ischemia, it is usually desirable to deliver oxygenated blood or oxygen-enriched fluids to at-risk tissues. Tissue injury is minimized or prevented by the diffusion of the dissolved oxygen from the blood or fluids to the tissue and/or blood perfusion that removes metabolites and that provides other chemical nutrients. [0010]
  • In some cases, the desired treatment of acute myocardial infarction and myocardial ischemia includes perfusion of oxygenated blood or oxygen-enriched fluids. During PTCA, for example, tolerated balloon inflation time may be increased by the concurrent introduction of oxygenated blood into the patient's coronary artery. Increased blood oxygen levels also may cause the normally perfused left ventricular cardiac tissue into hypercontractility to further increase blood flow through the treated coronary vessels. [0011]
  • The infusion of oxygenated blood or oxygen-enriched fluids also may be continued following the completion of PTCA treatment or other procedures (e.g. surgery) wherein cardiac tissue “stunning” with associated function compromise has occurred. In some cases continued infusion may accelerate the reversal of ischemia and facilitate recovery of myocardial function. [0012]
  • Conventional methods for the delivery of oxygenated blood or oxygen-enriched fluids to at-risk tissues involve the use of blood oxygenators. Such procedures generally involve withdrawing blood from a patient, circulating it through an oxygenator to increase blood oxygen concentration, and then delivering the blood back to the patient. One example of a commercially available blood oxygenator is the Maxima blood oxygenator manufactured by Medtronic, Inc., Minneapolis, Minn. [0013]
  • There are drawbacks, however, to the use of a conventional oxygenator in an extracorporeal circuit for oxygenating blood. Such systems typically are costly, complex and difficult to operate. Often a qualified perfusionist is required to prepare and monitor the system. [0014]
  • Conventional oxygenator systems also typically have a large priming volume, i.e., the total volume of blood contained within the oxygenator, tubing and other system components, and associated devices. It is not uncommon in a typical adult patient case for the oxygenation system to hold more than one to two liters of blood. Such large priming volumes are undesirable for many reasons. For example, in some cases a blood transfusion may be necessary to compensate for the blood temporarily lost to the oxygenation system because of its large priming volume. Heaters often must be used to maintain the temperature of the blood at an acceptable level as it travels through the extracorporeal circuit. Further, conventional oxygenator systems are relatively difficult to turn on and off. For instance, if the oxygenator is turned off, large stagnant pools of blood in the oxygenator might coagulate. [0015]
  • In addition, with extracorporeal circuits including conventional blood oxygenators there is a relatively high risk of inflammatory cell reaction and blood coagulation due to the relatively slow blood flow rates and the large blood contact surface area. A blood contact surface area of about 1-2 m[0016] 2 and velocity flows of about 3 cm/s are not uncommon with conventional oxygenator systems. Thus, relatively aggressive anti-coagulation therapy, such as heparinization, is usually required as an adjunct to using the oxygenator.
  • Perhaps one of the greatest disadvantages to using conventional blood oxygenation systems is that the maximum partial pressure of oxygen (pO[0017] 2) that can be imparted to blood with commercially available oxygenators is about 500 mm Hg. Thus, blood pO2 levels near or above 760 mm Hg cannot be achieved with conventional oxygenators.
  • Some experimental studies to treat myocardial infarction have involved the use of hyperbaric oxygen therapy. See, e.g., Shandling et al. (1997), [0018] Hyperbaric Oxygen and Thrombolysis in Myocardial Infarction: The “HOT MI” Pilot Study, American Heart Journal, Vol. 134, No. 3, pp. 544-550. These studies generally have involved placing patients in chambers of pure oxygen pressurized at up to 2 atmospheres, resulting in systemic oxygenation of patient blood up to a pO2 level of about 1200 mm Hg. However, use of hyperbaric oxygen therapy following restoration of coronary artery patency in the setting of an acute myocardial infarction is not practical. Monitoring critically ill patients in a hyperbaric oxygen chamber is difficult. Many patients become claustrophobic. Ear damage may occur. Further, treatment times longer than 90 minutes cannot be provided without concern for pulmonary oxygen toxicity.
  • For these reasons, the treatment of regional organ ischemia generally has not been developed clinically. Thus, there remains a need for a simple and convenient system for delivering oxygen-enriched blood and other fluids to patients for the localized prevention of ischemia and the treatment of post-ischemic tissue and organs. [0019]
  • SUMMARY OF THE INVENTION
  • The present invention may address one or more of the problems set forth above. Certain possible aspects of the present invention are set forth below as examples. It should be understood that these aspects are presented merely to provide the reader with a brief summary of certain forms the invention might take and that these aspects are not intended to limit the scope of the invention. Indeed, the invention may encompass a variety of aspects that may not be set forth below. [0020]
  • In one embodiment of the present invention, a system for the preparation and delivery of a gas-enriched fluid is provided. In applications involving the prevention of ischemia or the treatment of ischemic tissues, the system may be used for the preparation and delivery of an oxygen-enriched fluid including blood to a specific location within a patient's body. The system may include a circuit for oxygenating or enriching blood, e.g., increasing the level of dissolved oxygen in the blood. The system includes an apparatus that combines a gas-supersaturated fluid with blood to form a gas-enriched fluid, advantageously for regional or localized delivery. The gas-supersaturated fluid may include an oxygen-supersaturated physiologic liquid, and the blood to be enriched is blood withdrawn from the patient. [0021]
  • The system provided further includes assemblies for supplying controlled flows or supplies of the gas-supersaturated fluid and the blood. The system includes an elongated, generally tubular assembly including a central lumen and at least one end placeable within a patient body proximate a tissue site to be treated, the end including an outlet port for the gas-enriched fluid. The system may include a catheter defining a fluid pathway, including a proximal portion adapted for coupling to supplies of gas-supersaturated fluid and blood, and a distal portion defining a fluid pathway removably insertable within a patient's body, for infusing the gas-enriched fluid to predetermined sites. [0022]
  • In an alternate embodiment of the present invention, the proximal portion of the catheter is adapted for coupling to a supply of gas-supersaturated fluid, and includes a pump loop through which blood drawn from a blood inlet flows. The blood inlet comprises a porous side segment or axial sleeve defining the entry into an annular conduit that transitions into a lumen in fluid communication with the pump loop. The inlet is disposed along the portion of the catheter removably insertable within the patient's body. Upon insertion of the catheter through an access or opening, e.g., an introducer sheath, and upon its placement within the patient body, e.g., tip placement in or proximate the coronary ostium, the blood inlet is distal to the access sheath so as to permit blood from the patient to pass through and along the fluid path defined by the blood inlet, annular conduit, lumen and pump loop before combining with the gas-supersaturated fluid to form the gas-enriched fluid delivered to the patient via the catheter central lumen and outlet port. [0023]
  • In another embodiment of the present invention, a method is provided for the preparation and delivery of a gas-enriched fluid. In applications involving the prevention of ischemia or the treatment of ischemic tissues, the method may include the step of combining a gas-supersaturated fluid with blood to form a gas-enriched fluid. Advantageously, the gas-supersaturated fluid comprises an oxygen-supersaturated physiologic liquid in which oxygen is dissolved at concentrations normalized to standard temperature and pressure (STP) that equal or exceed the volume of the solvent. Examples of solvents which may be used include saline, lactated Ringer's, and other water-based physiologic solutions. [0024]
  • In accordance with another embodiment of the present invention, a method is provided for delivering an oxygen-enriched fluid to a specific site within a patient's body. The method comprises raising the pO[0025] 2 level of the fluid to be supplied to the patient. Where the fluid to be infused includes blood, the method may include the step of controlling or providing controlled amounts of the blood and oxygen-supersaturated fluid that are combined so as to produce an oxygen-enriched fluid for delivery to a specific predetermined site. Blood pO2 levels may be maintained, adjusted, or otherwise controlled by controlling the flow rates or by providing controlled amounts of the blood and/or oxygen-supersaturated fluid. Thus, a blood-gas control method is provided.
  • Furthermore, delivery of the gas-enriched fluid advantageously occurs without the formation of clinically significant bubbles. To help minimize or eliminate the formation of clinically significant bubbles, the blood contact surfaces are exposed to or coated with blood proteins for some brief time interval, usually at least several minutes, before the start of infusion of oxygen-supersaturated fluid. Also, fluid contact surfaces are exposed to or pre-wetted with liquids, e.g., saline, ethanol and benzalkonium heparin, before use. The fluid contact surfaces also do not include any substance which promotes such bubble formation, e.g., hydrophobic surfaces that are difficult to wet, teflon, teflon-composite liners, silicone oils, etc. Hydrophillic fluid contact surfaces are typically useful. [0026]
  • The embodiments may be used in conjunction with angiographic or guiding catheters, arterial sheaths, and/or other devices used in angioplasty and in other interventional cardiovascular procedures. The system may be used in applications involving one or more vascular openings, i.e., in either contralateral or ipsilateral procedures. [0027]
  • In contralateral procedures blood is withdrawn from the patient at a first location, e.g., the left femoral artery. The blood is enriched and then is returned to the patient at a second location proximate the tissue to be treated. Blood enrichment occurs as the blood pumped through the extracorporeal circuit or loop is combined with the gas-supersaturated fluid to form the gas-enriched fluid to be delivered. In applications where the system includes a catheter, the catheter may include proximal and distal ends and a central lumen. The proximal end is adapted for the catheter to receive a supply of the gas-supersaturated fluid and to receive the blood. The distal end is removably insertable within a patient's body through a second location such as the patient's right femoral artery. The distal end includes at least one port in fluid communication with the central lumen and through which the gas-enriched fluid may exit. Further, the distal portion of the catheter may be adapted with a tip portion shaped so as to promote insertion of the device, such as through the same sheath used for interventional procedures like angioplasty, to specific predetermined locations within a patient's body. Examples of tip portion shapes which may be used include any of the standard clinically accepted tip configurations used with devices like guide catheters for providing access to and for holding in locations like the coronary ostium. Accordingly, the method may further include the step of positioning the portion of the distal end of the catheter including the fluid exit port at a predetermined location within a patient body proximate to the tissue to be treated. [0028]
  • In ipsilateral procedures, the system may be used along with one or more of any of a number of suitable, standard-size, clinically accepted guide catheters and/or introducer sheaths. The system, for example, may comprise a catheter, a catheter and guide catheter, or a catheter and sheath, for use within a guide catheter or introducer sheath used for the primary interventional procedure. In accordance with this embodiment of the present invention, blood is drawn between the catheter and guide catheter or sheath assemblies of the present invention, between the catheter assembly of the present invention and the guide catheter or introducer sheath used for the primary interventional procedure, or from the annular space between the guide catheter and the introducer sheath. [0029]
  • As described herein, the preferred gas-supersaturated fluid for use in accordance with the present invention is an oxygen-supersaturated fluid. However, other fluids may be used depending upon the circumstances involved in a particular desired application, such as, for example, supersaturated fluids in which one or more gases such as helium, nitrous oxide, carbon dioxide and air are dissolved. The oxygen-supersaturated fluid may include a dissolved oxygen volume normalized to standard temperature and pressure of between about 0.5 and about 3 times the volume of the solvent. The fluid is supplied to the system at a pressure of between about 250 p.s.i. and about 5000 p.s.i. The exact pressure may vary depending upon the circumstances involved in a particular application. Further, the oxygen-supersaturated fluid supplied may be a sterile fluid which does not include gas, surface, or bubble nucleation sites at which clinically significant bubbles may form. [0030]
  • Exemplary apparatus and methods for preparing oxygen-supersaturated fluids are disclosed in U.S. Pat. No. 5,407,426 to Spears entitled “Method and Apparatus for Delivering Oxygen into Blood”; U.S. Pat. No. 5,569,180 to Spears entitled “Method for Delivering a Gas-Supersaturated Fluid to a Gas-Depleted Site and Use Thereof”; and U.S. Pat. No. 5,599,296 to Spears entitled “Apparatus and Method of Delivery of Gas-Supersaturated Liquids”; each of which is incorporated herein by reference. Furthermore, disclosure relating to exemplary apparatus and methods for the preparation and/or use of gas-supersaturated fluids, including, e.g., oxygen-supersaturated fluids, in various applications, may be found in the following patents and patent applications, each of which is incorporated herein by reference: [0031]
  • copending U.S. patent application Ser. No. 08/465,425, filed Jun. 5, 1995, which is a division of U.S. patent application Ser. No. 353,137, filed Dec. 9, 1994, now U.S. Pat. No. 5,599,296, which is a continuation in part of U.S. patent application Ser. No. 273,652, filed Jul. 12, 1994, now U.S. Pat. No. 5,569,180, which is a continuation in part of U.S. patent application Ser. No. 152,589, filed Nov. 15, 1993, now U.S. Pat. No. 5,407,426, which is a continuation in part of U.S. patent application Ser. No. 818,045, filed Jan. 8, 1992, now U.S. Pat. No. 5,261,875, which is a continuation of U.S. patent application serial no. [0032] 655,078, filed Feb. 14, 1991, now U.S. Pat. No. 5,086,620;
  • copending U.S. patent application Ser. No. 08/581,019, filed Jan. 3, 1996, which is a continuation in part of U.S. patent application Ser. No. 273,652, filed Jul. 12, 1994, now U.S. Pat. No. 5,569,180, which is a continuation in part of U.S. Patent application Ser. No. 152,589, filed Nov. 15, 1993, now U.S. Pat. No. 5,407,426, which is a continuation in part of U.S. patent application Ser. No. 818,045, filed Jan. 8, 1992, now U.S. Pat. No. 5,261,875, which is a continuation of U.S. patent application Ser. No. 655,078, filed Feb. 14, 1991, now U.S. Pat. No. 5,086,620; and [0033]
  • copending U.S. patent application Ser. No. 08/840,908, filed Apr. 16, 1997, which is a continuation in part of U.S. patent application [0034] 453,660, filed May 30, 1995, now U.S. Pat. No. 5,735,934, which is a division of U.S. patent application Ser. No. 273,652, filed Jul. 12, 1994, now U.S. Pat. No. 5,569,180, which is a continuation in part of U.S. Patent application Ser. No. 152,589, filed Nov. 15, 1993, now U.S. Pat. No. 5,407,426, which is a continuation in part of U.S. patent application Ser. No. 818,045, filed Jan. 8, 1992, now U.S. Pat. No. 5,261,875, which is a continuation of U.S. patent application Ser. No. 655,078, filed Feb. 14, 1991, now U.S. Pat. No. 5,086,620.
  • The catheter system of the present invention is typically sized in accordance with the circumstances involved in a particular application. In general, the sizes of the various system components will be on the order of the sizes of clinically accepted interventional cardiovascular devices. Usually, the extracorporeal loop of the present invention is less than four meters in total length. Thus, for example, where the system supports blood flow rates between 100 ml/min and 175 ml/min, the priming volume would be approximately 35 ml.[0035]
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • Further objects and advantages of the present invention will become apparent upon reading the following detailed description and upon referring to the accompanying drawings in which: [0036]
  • FIG. 1 is a schematic diagram of an exemplary embodiment of a catheter system used in a contralateral interventional procedure in accordance with the present invention. [0037]
  • FIG. 2 is a cross-sectional view of part of an exemplary embodiment of a catheter system including an angled blood flow path in accordance with the present invention. [0038]
  • FIG. 3 is a cross-sectional view of part of an alternate exemplary embodiment of a catheter system including an angled blood flow path in accordance with the present invention. [0039]
  • FIG. 4 is a cross-sectional view of part of another exemplary embodiment of a catheter system including a straight blood flow path in accordance with the present invention. [0040]
  • FIG. 4A is a cross-sectional view along line A-A in FIG. 4 of the exemplary embodiment of a catheter system including a straight blood flow path shown in accordance with the present invention. [0041]
  • FIG. 5 is a perspective view of part of an exemplary embodiment of a catheter system including an exemplary oxygen-supersaturated fluid outlet in accordance with the present invention. [0042]
  • FIG. 5A is a cross-sectional view along line A-A in FIG. 5 of the part of the exemplary embodiment of a catheter system including an exemplary oxygen-supersaturated fluid outlet shown in accordance with the present invention. [0043]
  • FIG. 5B is a view of the exemplary oxygen-supersaturated fluid outlet shown in FIG. 5 in accordance with the present invention. [0044]
  • FIG. 6 is a cross-sectional view of part of an exemplary embodiment of a catheter system including an integrated blood inlet introducer sheath in accordance with the present invention. [0045]
  • FIG. 7 is a schematic diagram of an exemplary embodiment of a catheter system for use in an ipsilateral interventional procedure in accordance with the present invention. [0046]
  • FIG. 8 is a cross-sectional view of part of an exemplary guide catheter including a liner used with an exemplary embodiment of a catheter system in accordance with the present invention. [0047]
  • FIG. 8A is a cross-sectional view of the exemplary guide catheter shown in FIG. 8, without the liner, in accordance with the present invention. [0048]
  • FIG. 9 is a cross-sectional view of part of an exemplary catheter system including an integral blood draw comprising a porous side blood inlet in accordance with the present invention. [0049]
  • FIG. 10 is a cross-sectional view of part of an exemplary catheter system including an integral blood draw comprising an axial blood inlet in accordance with the present invention. [0050]
  • FIG. 10A is a cross-sectional view along line A-A in FIG. 10 of the part of an exemplary catheter system shown in accordance with the present invention. [0051]
  • FIG. 11 is a view of part of an alternate exemplary catheter system including an integral blood draw comprising a porous side blood inlet in accordance with the present invention. [0052]
  • FIG. 11A is a cross-sectional view along line A-A in FIG. 11 of part of an alternate exemplary catheter system including an integral blood draw comprising a porous side blood inlet in accordance with the present invention. [0053]
  • FIG. 11B is a cross-sectional view along line B-B in FIG. 11 of part of an alternate exemplary catheter system including an integral blood draw comprising a porous side blood inlet in accordance with the present invention. [0054]
  • FIG. 11C is a cross-sectional view along line C-C in FIG. 11 of part of an alternate exemplary catheter system including an integral blood draw comprising a porous side blood inlet in accordance with the present invention. [0055]
  • FIG. 11D is a cross-sectional view along line D-D in FIG. 11 of part of an alternate exemplary catheter system including an integral blood draw comprising a porous side blood inlet in accordance with the present invention. [0056]
  • FIG. 12 is a cross-sectional view of an exemplary tip configuration of a catheter in accordance with the present invention. [0057]
  • FIG. 12A is a cross-sectional view along line A-A in FIG. 12 of an exemplary tip configuration of a catheter in accordance with the present invention. [0058]
  • FIG. 12B is a cross-sectional view along line B-B in FIG. 12 of an exemplary tip configuration of a catheter in accordance with the present invention. [0059]
  • FIG. 13 is a cross-sectional view of an alternate exemplary tip configuration of a catheter in accordance with the present invention. [0060]
  • FIG. 13A is a cross-sectional view along line A-A in FIG. 13 of an alternate exemplary tip configuration of a catheter in accordance with the present invention. [0061]
  • FIG. 13B is a cross-sectional view along line B-B in FIG. 13 of an alternate exemplary tip configuration of a catheter in accordance with the present invention. [0062]
  • FIG. 14 is a cross-sectional view of an alternate exemplary tip configuration of a catheter in accordance with the present invention. [0063]
  • FIG. 14A is a cross-sectional view of a further alternate exemplary tip configuration of a catheter in accordance with the present invention. [0064]
  • FIG. 15 is an isometric view of an exemplary bubble detector transducer in accordance with the present invention. [0065]
  • FIG. 15A is a partially exploded view of a portion of the bubble detector transducer shown in FIG. 15[0066]
  • The present invention may be susceptible to various modifications and alternative forms. Specific embodiments of the present invention are shown by way of example in the drawings and are described herein in detail. It should be understood, however, that the description set forth herein of specific embodiments is not intended to limit the present invention to the particular forms disclosed. Rather, all modifications, alternatives, and equivalents falling within the spirit and scope of the invention as defined by the appended claims are intended to be covered. [0067]
  • DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS
  • The description below illustrates embodiments of the present invention. For the sake of clarity, not all features of an actual implementation of the present invention are described in this specification. It should be appreciated that in connection with developing any actual embodiment of the present invention many application-specific decisions must be made to achieve specific goals, which may vary from one application to another. Further, it should be appreciated that any such development effort might be complex and time-consuming, but would still be routine for those of ordinary skill in the art having the benefit of this disclosure. [0068]
  • For the sake of clarity and convenience, the various embodiments are described herein in the context of interventional cardiovascular applications generally involving acute or transient ischemia or post-ischemic tissues. However, the present invention may also useful in other medical applications, such as cancer therapy (e.g., the delivery of oxygen-enriched fluids directly into poorly vascularized tumors during radiation or chemotherapy treatments), neurovascular applications (e.g., the treatment of stroke and cerebral trauma patients), lung support in trauma and lung disease patients, and wound care management. [0069]
  • Also, although the present invention may be used to raise oxygen levels, for example, in venous and arterial blood, in blood substitutes, e.g., perfluorocarbons, and in combinations thereof, for the sake of clarity and convenience reference is made herein only to arterial blood. [0070]
  • Further, the present invention also may be used in connection with drug fluid infusion therapies. Examples of drug fluids used in cardiovascular and neurological procedures which may be infused in accordance with the present invention include, without limitation, vasodilators (e.g., nitroglycerin and nitroprusside), platelet-actives (e.g., ReoPro and Orbofiban), thrombolytics (e.g., t-PA, streptokinase, and urokinase), antiarrhythmics (e.g., lidocaine, procainamide), beta blockers (e.g., esmolol, inderal), calcium channel blockers (e.g., diltiazem, verapamil), magnesium, inotropic agents (e.g., epinephrine, dopamine), perofluorocarbons (e.g., fluosol), crystalloids (e.g., normal saline, lactated ringers), colloids (albumin, hespan), blood products (packed red blood cells, platelets, whole blood), Na+/H+ exchange inhibitors, free radical scavengers, diuretics (e.g., mannitol), antiseizure drugs (e.g., phenobarbital, valium), and neuroprotectants (e.g., lubeluzole). [0071]
  • Turning now to the drawings, a system is provided in which blood is combined with an oxygen-supersaturated fluid to form an oxygen-enriched fluid that may be delivered to a particular predetermined area within a patient's body for the treatment of conditions such as tissue ischemia and post-ischemic tissues. As shown in FIG. 1, one embodiment of such a [0072] system 10 includes a blood draw 12 comprising a continuous fluid flow path between a vascular access site 14 of a patient body and a pump 16. The selection of the vascular access site typically is made by a physician or caregiver and depends upon the circumstances surrounding the particular application involved. The particular vascular access site illustrated in FIG. 1 is the left femoral artery. The blood pump 16 may be one of the many commercially available and clinically accepted blood pumps suitable for use with human patients. An example of one such pump is the Model 6501 RFL3.5 Pemco peristaltic pump available from Pemco Medical, Cleveland, Ohio.
  • The [0073] pump 16 draws blood from the patient and provides a supply of blood via line 18 to the inlet 20 of catheter 22. The flow characteristics of the blood will depend upon the circumstances surrounding the particular application involved. Typically, the supply of blood to the blood inlet 20 of catheter 22 will be a controlled flow defined by the flow parameters selected by the caregiver. Factors influencing the determination of blood flow characteristics may include one or more of the many clinical parameters or variables of the blood to be supplied to the catheter or of the oxygen-enriched fluid to be delivered to the patient, e.g., the size of the patient, the percentage of overall circulation to be provided, hemolysis, hemodilution, pO2, pulsatility, mass flow rate, volume flow rate, temperature, hemoglobin concentration and pH.
  • The [0074] system 10 may include one or more gas bubble detectors, at least one of which is capable of detecting the presence of microbubbles, i.e., bubbles with diameters of about 7 to 10 microns to about 200 microns (see, e.g., FIG. 12). In addition, the system may include one or more macrobubble detectors to detect larger bubbles, such as bubbles with diameters of 1 millimeter or more. Such macrobubble detectors may comprise any suitable commercially available detector, such as an outside, tube-mounted bubble detector including two transducers measuring attenuation of a sound pulse traveling from one side of the tube to the other. One such suitable detector may be purchased from Transonic Inc. of New York. The microbubble and macrobubble detectors provide the physician or caregiver with a warning of potentially clinically significant bubble generation. The system 10 also may include various conventional items, such as sensors, flow meters (which may also serve a dual role as a macrobubble detector), or other clinical parameter monitoring devices; hydraulic components such as accumulators and valves for managing flow dynamics; access ports which permit withdrawal of fluids; filters or other safety devices to help ensure sterility; or other devices that generally may assist in controlling the flow of one or more of the fluids in the system 10. Advantageously, any such devices are positioned within the system and used so as to avoid causing the formation of clinically significant bubbles within the fluid flow paths.
  • The [0075] catheter 22 includes a proximal portion 24 and a distal portion 26, the distal portion being removably insertable within a patient body through a vascular access or opening 36. The proximal portion 24 includes blood inlet 20. Blood inlet 20 and line 18 may be adapted for releasably coupling, e.g., with a clinically accepted fluid connection apparatus such as a Luer lock, to enable the catheter 22 to receive the blood supplied via line 18. The catheter 22 includes a lumen defining a continuous blood flow path from the blood inlet 20 to a fluid exit port proximate the distal tip 28 of catheter 22.
  • The [0076] proximal portion 24 of catheter 22 also includes a fluid inlet port 30 adapted to couple to a supply 32 of oxygen-supersaturated fluid. The port 30 is in fluid communication with the supply 32 and with line 34. Line 34 comprises one or more capillaries or other elongated generally tubular members including central lumens, either alone or in an array, each defining a continuous fluid flow path between port 30 and the blood flow path of the catheter 22.
  • The oxygen-supersaturated fluid is usually supplied to [0077] port 30 in accordance with parameters specified and selected by the caregiver for the desired clinical indication. The flow of oxygen-supersaturated fluid is generally steady and continuous, although variable or intermittent flows may be used. Flow rates may range from about 0.1 cc/min to about 40 cc/mm, although particularly advantageous flow rates may be between about 2 cc/min and 12 cc/min. Oxygen concentrations may range from about 0.5 cc O2 per cc physiologic solution to about 3 cc O2 per cc physiologic solution, although particularly advantageous concentrations may be about 1 cc O2 per cc physiologic solution. The oxygen-supersaturated fluid is provided at a temperature such that when the fluid combines with blood to form the oxygen-enriched fluid to be infused, the oxygen-enriched fluid is about 37° C., i.e., system operation does not significantly affect patient blood temperature.
  • FIG. 2 shows an embodiment in which [0078] catheter portion 40 comprises a section of the catheter in which the flows of blood and oxygen-supersaturated fluid combine. Catheter portion 40 comprises the proximal end of an elongated tubular member 48, including a generally centrally disposed fluid return lumen 52, disposed within a housing 42 including a blood inlet lumen 44. Lumen 44 defines a continuous fluid flow path between catheter blood inlet port 46 and the proximal end 50 of fluid return lumen 52. The distal portion of member 48 (not shown) is removably insertable within a patient body and includes the exit port through which fluid traveling within fluid return lumen 52 is delivered to a site within a patient's body.
  • [0079] Housing 42 typically comprises a biocompatable, molded polymeric material. The exact size and shape of housing 42 may vary depending upon the circumstances involved in a particular application. FIG. 2, by way of example, shows a generally y-shaped configuration. The tubular member 48 may be integrally formed with housing 42. However, tubular member 48 may comprise clinically approved polymeric tubing. The proximal end of member 48 is fixedly attached within housing 42. Typically, the joining of housing 42 and member 48 is accomplished by solvent or adhesive bonding or insert or over molding.
  • The size and shape of [0080] lumen 44 also may vary depending upon the circumstances involved in a particular application. FIG. 2, by way of example, shows a lumen 44 defining an angled blood flow path. However, a straight or curved blood flow path might also be used. See, e.g., FIG. 4. Advantageously, any difference between the inner diameter of the proximal end of member 48 and the diameter of lumen 44 at the proximal end 50 of fluid return lumen 52 is minimized or eliminated to promote smooth blood flow.
  • [0081] Catheter portion 40 also includes the distal portion of an oxygen-supersaturated fluid delivery line 54. The line 54 comprises at least one elongated generally tubular member including a central lumen defining a fluid flow path between a fluid inlet port (not shown in FIG. 2) disposed at the proximal end of line 54 and fluid exit port 56 disposed at the distal end 58 of line 54. Catheter portion 40 also may include one or more stress/ strain relief assemblies 60, 62.
  • The proximal end of [0082] line 54 may be adapted to releasably couple to a supply of oxygen-supersaturated fluid. The fluid exit port 56 may be disposed within the flow path defined by fluid return lumen 52. Thus, a continuous fluid flow path is defined between the supply of oxygen-supersaturated fluid and a predetermined site within a patient's body proximate the distal end of fluid return lumen 52.
  • The portions proximate to [0083] fluid exit port 56 of fluid return lumen 52 and of the distal end 58 of line 54 are generally straight, and their longitudinal axes approximately coincide, so that any difference in the direction of blood flow in lumen 52 proximate port 56 and the direction of exit fluid flow through port 56 is minimized or eliminated.
  • As shown in FIG. 2, [0084] fluid exit port 56 may be sufficiently downstream of the proximal end 50 of fluid return lumen 52 that the fluid exiting port 56 avoids any fluid flow disruption or non-laminar flow associated with the boundary between housing 42 and member 48 that might cause the formation of clinically significant gas bubbles. However, where any such flow disruptions or non-laminar flows are minimized or eliminated, the exit port for the oxygen-supersaturated fluid may be disposed upstream of the proximal end of the fluid return lumen. See, e.g., FIGS. 3 and 4. Further, as shown in FIG. 3, in an alternate embodiment, an oxygen-supersaturated fluid line 64 may include a distal portion 66 including a fluid exit port 68 at the outer boundary of lumen 44. For example, as shown in FIG. 3, the longitudinal axis of line 64 proximate port 68 and the longitudinal axis of the portion of lumen 44 downstream of port 68 advantageously coincide, while the longitudinal axis of line 64 proximate port 68 and the longitudinal axis of the portion of lumen 44 upstream of port 68 advantageously form an angle 70 comprising an acute angle which permits the smooth introduction of fluid from line 64 into the blood flow through lumen 44. Advantageously, the angle 70 may be about thirty degrees, for instance.
  • As shown in FIG. 2, the portion of [0085] line 54 extending from housing 42 into the blood flow path may be rigid enough to comprise a cantilever-like member. However, as shown in FIG. 4, the extending portion of the oxygen-supersaturated fluid flow line 76 also may comprise a more flexible member which tends to align itself naturally within blood flow lumen 74 along the path of least resistance. The distal end of line 76 may be supported in place or otherwise oriented within the lumen 74 by one or more wings 72 extending between the distal end of oxygen-supersaturated line 76 and the outer wall or boundary defining lumen 74. The flexibility and positioning of the lines 54 and 76 depend upon the circumstances involved in a particular application, e.g., the material hardness, line profile, the number of capillaries making up the line, and the desired fluid exit location.
  • The oxygen-supersaturated fluid is injected so as to minimize or avoid altogether blood cell damage. An exemplary oxygen-supersaturated fluid outlet is shown in FIG. 5. The oxygen-supersaturated [0086] fluid line 80 is disposed within fluid delivery lumen 84. The distal tip of line 80 is oriented within lumen 84 by one or more ribs or spacers 82 securing the distal portion of line 80. The line 80 includes one or more capillaries 86 (see FIG. 5B) each including a central lumen 88 through which oxygen-supersaturated fluid flows. The configuration of the distal tip of line 80 advantgeously minimizes or eliminates flow disruptions resulting from the exit of fluid from each lumen 88 into the flow of blood within lumen 84. By way of example, FIG. 5B shows a line 80 comprising four capillaries 86 and including a distal tip of generally conical shape. The ends of each capillary 86 may form an included angle 90 of about 52 degrees, for instance. The capillaries may be made of glass sheathed in polyimide, with ground and polished distal ends to help minimize or eliminate the formation of clinically significant bubbles and fluid flow disruptions. The line 80 may include four 100 micron inner diameter by 350 micron outer diameter tubes, for instance, potted together with epoxy at their proximal and distal ends. However, the inner diameter may be in the range of about 20 to about 1000 microns, with an inner diameter of about 100 to about 125 microns being particularly advantageous. Of course the exact size and shape of the distal end and tip of line 80 may vary depending upon the circumstances involved in a particular application. Examples of possible configurations include, without limitation, flat, blunt, squared, pencil-shaped, curved, parabolic, hyperbolic, and pyramidal.
  • In the embodiment shown in FIG. 6, the catheter includes an oxygen-enriched [0087] fluid return line 100 and a blood draw assembly comprising a sheath 102 and housing 104. The housing 104 includes a lumen 106 which forms a blood flow path between the lumens of sheath 102 and tube 108. Tube 108 comprises the line which supplies blood to the blood pump (not shown in FIG. 6) of the system. The line 100 is generally centrally disposed through the housing 104 and within the central lumen of the sheath 102. Upon insertion of the distal portion of line 100 into a patient's body, the sheath 102 is positioned within a vascular access sheath, guide catheter, or other such access device, so that blood from the patient may enter the annular space 110 between the outer wall of line 100 and the inner wall of sheath 102. The proximal end of line 100 may include a stress/strain relief assembly 112.
  • FIG. 7 is a schematic diagram illustrating a use of the catheter system with a separate [0088] arterial access sheath 114. The sheath 114 may be one of the many sizes and types of clinically accepted arterial access sheaths suitable for use in interventional cardiovascular procedures. The proximal end 116 of sheath 114 is adapted with a seal or other such device which permits the insertion of catheters, guidewires, or other interventional devices through the sheath 114 and into the body without unnecessary loss of blood. Blood drawn through the lumen 118 of sheath 114 travels via line 120 to blood pump 122 before being enriched and returned to the body. The blood returns via line 124 and the catheter portion 126, where the blood flow combines with a flow of oxygen-supersaturated fluid delivered via line 128 from a supply 130 to form the oxygen-enriched fluid delivered to the patient via the distal portion 132 of the catheter system.
  • FIGS. 8 and 8A show an alternate embodiment of the catheter system. In accordance with this embodiment, a [0089] guide catheter 140 including a distal tip (not shown) removably insertable within a patient's body is placed through an outer arterial access sheath 142. The sheath 142 may be any one of the many types of clinically accepted sheaths typically used in interventional cardiovascular procedures to gain access to a patient's vasculature. The guide catheter 140 includes a liner 144. The liner 144 is deformable and may be either partially (not shown) or completely (see FIG. 8A) removed. When a positive pressure is applied to lumen 146 of guide catheter 140, e.g., when angiographic dyes are introduced into the lumen 146, and when the liner 144 is in place covering the blood inlet holes 148 through the wall of guide catheter 140, the liner 144 presses against and closes inlet holes 148. When a negative pressure is applied to lumen 146 of guide catheter 140, e.g., during the withdrawal of blood from the patient, the liner deforms as necessary to allow the entry of blood into lumen 146 through inlet holes 148.
  • To facilitate the draw of blood from the patient, the [0090] fluid return line 150 may include a proximal portion 152 having smaller internal and external diameters than the distal portion 154 of line 150. When the distal tip of line 150 (not shown) is in place within the patient's body proximate a predetermined site, the transition region 156 is disposed downstream of blood inlet holes 148 so as to permit the entry of blood into lumen 146. The transition region 156 comprises a section of the line 150 in which the external and internal diameters of the line 150 increase along its length. To minimize or eliminate the formation of clinically significant bubbles, downstream of transition region 156 the flow of blood in line 150 combines with oxygen-supersaturated fluid exiting at the end 158 of oxygen-supersaturated fluid supply tube 160. As described herein (see, e.g., FIG. 5), the tube 160 may comprise either a single capillary or tube, or a bundle of capillaries or tubes.
  • FIG. 9 describes part of a catheter system including an integral blood draw comprising an annular porous [0091] side blood inlet 170. The catheter 172 may be used along with a guide catheter or access sheath (not shown in FIG. 9). Blood is drawn from the patient and through the inlet 170 into catheter outer lumen 174. From there, the blood circulates through a blood pump and is delivered back to the patient via catheter inner lumen 176. As shown in FIG. 9, the inner lumen 176 includes a proximal portion 178 having relatively smaller internal and external diameters than distal portion 180, and a transition region 182 joining the two portions. Oxygen-supersaturated fluid supply tube 184 includes a fluid exit port 186 disposed within the distal portion 180 of catheter 172. The fluid exiting tube 184 enters the blood flow within lumen 176 downstream of any sharp pressure drops or other flow disturbances associated with the increase in the inner diameter of lumen 176 in the transition region 182. Ribs or wings 188 or another such centering device may be used to hold the distal portion of tube 184 in place.
  • In an alternate embodiment, as shown in FIG. 10, the integral blood inlet of a [0092] catheter 190 comprises an axial blood inlet 192. Blood from the patient is drawn from the interior of a guide catheter or sheath, or directly from the patient's vasculature, through the inlet 192, and into catheter outer lumen 194. From there the blood travels through a blood pump (not shown) and is returned to the patient via inner lumen 196. As shown in FIG. 10, the inner lumen 196 includes a proximal portion 198 having relatively smaller internal and external diameters than distal portion 200, and a transition region 202 joining the two portions. Oxygen-supersaturated fluid supply tube 204 includes a fluid exit port 206 disposed within the distal portion 200 of catheter 190, and ribs or wings 208 may be used to hold the distal portion of tube 204 in place. The proximal portion 198 of inner lumen 196 may be fixed within the interior of outer lumen 194 by a further set or ribs or wings or other similar positioning device. As shown in FIG. 10, the proximal portion 198 of lumen 196 is free to naturally follow a path of least resistance through lumen 194. The proximal portion of tube 204 likewise may be secured within lumen 196 or be free as shown.
  • FIGS. 11 and 11A-D show part of an alternate exemplary catheter system including an integral blood draw. A porous side blood inlet [0093] 210 comprising a plurality of channels 212 through the outer wall of catheter 214 allows blood from the patient to enter outer lumen 216. The blood in lumen 216 passes through a blood pump (not shown in FIG. 11) before returning to the patient via lumen 218. Within lumen 218 the blood combines with an oxygen-supersaturated fluid supplied via a tube 220. As shown in FIG. 11, the tube 220, along at least a portion of its length, may be disposed within the lumen 218. The distal tip of the tube 220 is positioned along the longitudinal axis of lumen 218 and secured in place by one or more centering fins or spacers 222.
  • The [0094] catheter 214 also may include a lumen 224 through which blood proximate the distal tip 226 of the catheter 214 may be drawn, e.g., to provide a blood sample for use in determining blood pO2 or in the monitoring of others clinical parameters, to ascertain blood pressure at the distal end of the catheter, etc.
  • The [0095] distal tip 226 of catheter 214 includes an ultrasonic bubble detector 228 or similar assembly for detecting the presence of clinically significant bubbles in the oxygen-enriched fluid delivered to the patient body via lumen 218. Accordingly, the catheter 214 may also include one or more lumens 230 within which leads coupled to the bubble detector 228 are disposed. 5
  • FIGS. [0096] 12-14 illustrate alternate exemplary tip configurations of a catheter. FIG. 12 shows a straight tip portion 232 including a bubble detector 236 disposed proximate the tip 234 of the catheter. Bubble detector leads 238 comprising one or more pairs of insulated wires or coaxial wires may be disposed as shown for example in FIG. 12A within the catheter side wall. FIG. 13 illustrates a straight tip portion 240 including a dual transducer bubble detector 242, bubble detector leads 244, and a monorail guide lumen 246 through which a guidewire (not shown) may be thread to assist in the placement of the catheter within a patient body. One transducer of a dual transducer bubble detector typically emits an acoustic pulse which is received by the other transducer, and the presence or absence of bubbles is determined by measuring the attenuation of the received signal. FIGS. 14 an 14A illustrate alternate configurations of a catheter tip including a monorail guide lumen 248. The catheter tip as shown in the drawings may include a relatively uniform wall thickness and be of generally circular cross section (FIG. 14), or it may have a varying wall thickness and assume a more tear-drop shape (FIG. 14A).
  • As shown in FIG. 12, a catheter tip also may include a [0097] radiopaque band 250 to aid the physician or caregiver in placing the device. Typically, the band 250 comprises one or more metals or metal alloys, e.g., platinum, gold, tungsten, and iridium, and platinum-iridium and other high density materials that are visible under fluoroscopy.
  • A further exemplary [0098] bubble detector transducer 252 is shown in FIGS. 15 and 15A. The transducer 252, which may be bonded or otherwise fixedly attached to or within the distal portion of the catheter, may include a single transducer operable in a pulse echo mode, i.e., it can send out an acoustic pulse and sense its reflection. The transducer 252 includes an inner sleeve 254, a layer of wrapped piezo-electric film 256, a metal band 258, and an outerjacket 260. The inner sleeve 254 comprises a polyimide sleeve. The wrapped film 256 comprises a metallized polyvinylidenefluoride (PVDF) film including a conductive upper layer 262, a conductive lower layer 264, and an insulative inner layer 263 separating the upper and lower layers. As shown in the drawings, the metallized film is folded and then wrapped at least once (typically about two to five times) about the inner sleeve 254. This folding permits the use of thinner film that exhibits higher capacitance and lower impedance than a more conventional transducer so that the wire leads 266, which are long, thin wires, may be driven better. Wire leads 266 are connected to the outermost surfaces of the layers 262, 264 with a conductive epoxy 268. The band 258 may comprise a foil of aluminum or a band of a metal which reflects the outward acoustic pulse. The band 258 comprises a radiopaque material so that the band may also act as a marker to promote placement of the device. The outer jacket 260 may be made of pebax or another suitable material which provides support to the structure. It should further be understood that the bubble detector illustrated in FIGS. 15 and 15A is advantageously a compact device, e.g., air spaces between the layers of the bubble detector are minimized or eliminated. For example, any air voids may be filled with an epoxy or other suitable filler material.
  • The [0099] electronic circuitry 271 associated with the bubble detector transducer 252 causes the transducer 252 to emit ultrasonic pulses typically in the range of 20-30 MHz. In the pulse echo mode, these ultrasonic pulses are transmitted in a pulse train having a frequency of about 20-50 kHz. Thus, approximately ten reflections may be sampled from a single bubble as it passes by the transducer 252, which is about 1 to 1.5 millimeters in length. After the pulses of ultrasonic energy are delivered during a positive portion of this duty cycle, the circuitry 271 waits approximately 0.5 microseconds to allow for a “ring down” period. Then, the reflected signals may be measured, typically for at least three bounces, before the next ultrasonic signals are transmitted.
  • The present invention has been described in terms of exemplary embodiments. In accordance with the present invention, the operating parameters for the system may be varied, typically with a physician or caregiver specifying and selecting them for the desired clinical indication. Further, it is contemplated that other embodiments, which may be readily devised by persons of ordinary skill in the art based on the teachings set forth herein, may be within the scope of the invention which is defined by the appended claims. The present invention may be modified and practiced in different but equivalent manners that will be apparent to those skilled in the art having the benefit of the teachings set forth herein. [0100]
  • No limitations are intended to the details or construction or design shown herein, other than as described in the claims appended hereto. Thus, it should be clear that the specific embodiments disclosed above may be altered and modified, and that all such variations and modifications are within the spirit and scope of the present invention as set forth in the claims appended hereto. [0101]

Claims (49)

What is claimed is:
1. An apparatus for the preparation of a gas-enriched fluid, the apparatus comprising:
means for supplying a first fluid comprising a gas-supersaturated liquid;
means for supplying a second fluid; and
means for combining the first and second fluids to form the gas-enriched fluid.
2. The apparatus of claim 1 wherein the combining means comprises a catheter including a central lumen in fluid communication with the means for supplying the first and second fluids.
3. The apparatus of claim 1 wherein the first fluid comprises an oxygen-supersaturated fluid.
4. An apparatus for the preparation of a gas-enriched fluid, the apparatus comprising:
an assembly including first and second lumens;
the first lumen in fluid communication with a first fluid supply; and
the second lumen in fluid communication with a second fluid supply of a gas-supersaturated fluid and with the first lumen.
5. The apparatus of claim 4 wherein the second fluid comprises an oxygen-supersaturated fluid.
6. The apparatus of claim 4 wherein a portion of the assembly is removably insertable within a patient's body.
7. The apparatus of claim 4 wherein the gas-enriched fluid is a physiologic solution.
8. The apparatus of claim 4 wherein the gas-enriched fluid comprises blood.
9. The apparatus of claim 4 wherein the gas-enriched fluid comprises oxygen-enriched blood.
10. The apparatus of claim 4 wherein the gas-enriched fluid comprises an oxygen-supersaturated fluid and blood.
11. The apparatus of claim 4 wherein the gas-enriched fluid comprises a blood substitute.
12. The apparatus of claim 4 wherein the gas-enriched fluid comprises blood plasma.
13. An apparatus for the delivery of a gas-enriched fluid to a site, the apparatus comprising:
a first assembly comprising an elongated generally tubular member including proximal and distal ends and a lumen comprising a continuous fluid flow path between the proximal and distal ends, the distal end disposed proximate to the site to which the gas-enriched fluid is to be delivered; and
a second assembly comprising at least one elongated generally tubular member including first and second ends and at least one lumen comprising a continuous fluid flow path between the first and second ends, the second end disposed within the lumen of the first assembly, the first end of the second assembly adapted to be coupled to a supply of a first fluid, the first fluid comprising a gas-supersaturated fluid, and the proximal end of the first assembly adapted to be coupled to a supply of a second fluid.
14. The apparatus of claim 13 wherein the second assembly comprises a plurality of elongated generally tubular members, each member including first and second ends and at least one lumen comprising a continuous flow path between the first and second ends, the second ends disposed within the lumen of the first assembly.
15. The apparatus of claim 13 wherein the second assembly lumen has an internal diameter of between about 20 microns and 1000 microns.
16. The apparatus of claim 13 wherein the second assembly lumen has an internal diameter of between about 100 microns to 125 microns.
17. The apparatus of claim 13 wherein at least a portion of the first assembly including the distal end is removably insertable within a patient's body.
18. The apparatus of claim 17 wherein the removably insertable portion is insertable through a body access port.
19. The apparatus of claim 18 wherein the body access port comprises a guiding catheter.
20. The apparatus of claim 18 wherein the body access port comprises a sheath.
21. An apparatus for increasing fluid oxygen levels, the apparatus comprising:
means for providing a supply of a first fluid;
means for providing a supply of a second fluid comprising a gas-supersaturated liquid; and
an assembly including first and second lumens, the first lumen in fluid communication with the first fluid supply means, the second lumen in fluid communication with the second fluid supply means and with the first lumen.
22. The apparatus of claim 21 wherein the first fluid comprises blood.
23. The apparatus of claim 22 wherein the oxygen level increased is the level of dissolved oxygen in the blood.
24. The apparatus of claim 21 wherein the oxygen level increased is the oxygen saturation level of an oxygen carrier.
25. The apparatus of claim 24 wherein the oxygen carrier is hemoglobin.
26. The apparatus of claim 24 wherein the oxygen carrier is a blood substitute.
27. The apparatus of claim 22 wherein the oxygen level increased is the concentration of oxygen in the blood.
28. The apparatus of claim 22 wherein the oxygen level increased is the blood partial pressure of oxygen.
29. The apparatus of claim 21 wherein the means for providing a supply of a first fluid comprise a means for withdrawing blood from a patient body.
30. The apparatus of claim 21 wherein the means for providing a supply of a first fluid includes a blood pump.
31. A catheter comprising:
a first elongated generally tubular member including proximal and distal ends, the first member including a lumen comprising a continuous fluid pathway between the proximal and distal ends; and
a second elongated generally tubular member including proximal and distal ends, the second member coupled to the first member, the second member including a lumen comprising a continuous fluid pathway between the proximal end of the second member and the fluid pathway between the proximal and distal ends of the first member.
32. The catheter of claim 31 wherein a portion of the first member proximate to its distal end is removably insertable into a patient's body.
33. The catheter of claim 32 wherein the insertable portion of the first member includes at least one port in fluid communication with the fluid pathway between the proximal and distal ends of the first member.
34. The catheter of claim 32 wherein the proximal end of the first member is adapted to provide a continuous fluid pathway between a supply of blood and the fluid pathway between the proximal and distal ends of the first member.
35. The catheter of claim 32 wherein the proximal end of the second member is adapted to provide a continuous fluid pathway between a supply of gas-supersaturated fluid and the fluid pathway between the proximal end of the second member and the fluid pathway between the proximal and distal ends of the first member.
36. A catheter comprising:
a first elongated generally tubular member including proximal and distal ends, the first member including a lumen comprising a continuous fluid pathway between the proximal and distal ends; and
a plurality of side members, each side member comprising an elongated generally tubular member including proximal and distal ends, the side members coupled to the first member, each side member including a lumen comprising a continuous fluid pathway between the proximal ends of the side members and the fluid pathway between the proximal and distal ends of the first member.
37. A device for combining a first fluid with a second gas-supersaturated fluid, the device comprising:
a housing having therein a first fluid passageway having a first end and a second end and a second fluid passageway having a first end and a second end, the second end of the second fluid passageway intersecting the first fluid passageway at a junction between the first and second ends of the first fluid passageway, the first end of the first fluid passageway being adapted to receive a first line for supplying the second gas-supersaturated fluid, and the first end of the second fluid passageway being adapted to receive a supply of the first fluid, the first line having an outlet positioned in a substantially laminar flow region of the first fluid passageway.
38. The device of claim 37, wherein the second end of the first fluid passageway is adapted to receive a proximal end of a first catheter, the first catheter having a distal end adapted to be positioned within a patient's body for delivering a combination of the first fluid and the second gas-supersaturated fluid to a site within the patient's body.
39. The device of claim 38, wherein the outlet of the first line is positioned downstream from the proximal end of the first catheter.
40. The device of claim 38, wherein the outlet of the first line is positioned upstream from the proximal end of the first catheter.
41. The device of claim 37, wherein the outlet of the first line is positioned between the junction and the second end of the first fluid passageway.
42. The device of claim 37, wherein the outlet of the first line is positioned between the first end of the first fluid passageway and the junction.
43. The device of claim 37, wherein the outlet of the first line is positioned at the junction.
44. The device of claim 37, wherein the first line comprises a plurality of wings for supporting the first line within the first fluid passageway.
45. The device of claim 37, wherein the first fluid passageway is angled relative to the second fluid passageway at an acute angle.
46. The device of claim 37, wherein the first fluid comprises blood and wherein the second fluid comprises oxygen-supersaturated fluid.
47. The device of claim 37, further comprising a pump coupled to supply the first fluid to the second fluid passageway.
48. The device of claim 47, comprising a second catheter having a proximal end and a distal end, the proximal end being coupled to an inlet of the pump, and the distal end being adapted to be positioned within a patient's body for delivering the first fluid from the patient's body to the pump, and comprising a tube coupled between an outlet of the pump and the first end of the second fluid passageway for delivering the first fluid to the second fluid passageway.
49. The device of claim 38, further comprising a microbubble detector disposed proximate the distal end of the first catheter.
US10/213,650 1997-08-15 2002-08-06 Apparatus for the preparation and delivery of gas-enriched fluids Abandoned US20020192111A1 (en)

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US09/122,438 US6454997B1 (en) 1997-08-15 1998-07-24 Apparatus for the preparation and delivery of gas-enriched fluids
US10/213,650 US20020192111A1 (en) 1997-08-15 2002-08-06 Apparatus for the preparation and delivery of gas-enriched fluids

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US09/122,438 Expired - Lifetime US6454997B1 (en) 1997-08-15 1998-07-24 Apparatus for the preparation and delivery of gas-enriched fluids
US09/239,076 Expired - Lifetime US6248087B1 (en) 1997-08-15 1999-01-27 Apparatus for generalized extracorporeal support
US09/741,625 Expired - Fee Related US6746417B2 (en) 1997-08-15 2000-12-19 Apparatus for generalized extracorporeal support
US10/213,650 Abandoned US20020192111A1 (en) 1997-08-15 2002-08-06 Apparatus for the preparation and delivery of gas-enriched fluids

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US09/122,438 Expired - Lifetime US6454997B1 (en) 1997-08-15 1998-07-24 Apparatus for the preparation and delivery of gas-enriched fluids
US09/239,076 Expired - Lifetime US6248087B1 (en) 1997-08-15 1999-01-27 Apparatus for generalized extracorporeal support
US09/741,625 Expired - Fee Related US6746417B2 (en) 1997-08-15 2000-12-19 Apparatus for generalized extracorporeal support

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6849235B2 (en) 1999-09-30 2005-02-01 Therox, Inc. Method of forming gas-enriched fluid
WO2008042721A2 (en) * 2006-09-29 2008-04-10 Zevex, Inc. Method and apparatus for detecting air bubbles
US20080098798A1 (en) * 2006-10-24 2008-05-01 Riley Timothy A Method for making and using an air bubble detector
US7987722B2 (en) 2007-08-24 2011-08-02 Zevex, Inc. Ultrasonic air and fluid detector
US8303613B2 (en) 2007-12-07 2012-11-06 Zevex, Inc. Ultrasonic instrument using langevin type transducers to create transverse motion
US8539812B2 (en) 2009-02-06 2013-09-24 Zevek, Inc. Air bubble detector

Families Citing this family (130)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6607698B1 (en) * 1997-08-15 2003-08-19 Therox, Inc. Method for generalized extracorporeal support
US6702949B2 (en) 1997-10-24 2004-03-09 Microdiffusion, Inc. Diffuser/emulsifier for aquaculture applications
DE19757224A1 (en) * 1997-12-22 1999-07-01 Bayer Ag Method and device for in-situ formulation of a drug solution for parenteral administration
US6602467B1 (en) 1998-07-24 2003-08-05 Therox, Inc. Apparatus and method for blood oxygenation
AU5126499A (en) * 1998-07-24 2000-02-14 Therox, Inc. Method and apparatus for the preparation and delivery of gas-enriched fluids
US6533766B1 (en) * 1998-07-24 2003-03-18 Therox, Inc. Coating medical device surfaces for delivering gas-supersaturated fluids
US8506519B2 (en) 1999-02-16 2013-08-13 Flowcardia, Inc. Pre-shaped therapeutic catheter
US6855123B2 (en) 2002-08-02 2005-02-15 Flow Cardia, Inc. Therapeutic ultrasound system
JP4331869B2 (en) * 1999-06-24 2009-09-16 株式会社根本杏林堂 Autologous blood perfusion device for coronary artery bypass surgery under heart beat
US6387324B1 (en) 1999-09-30 2002-05-14 Therox, Inc. Apparatus and method for blood oxygenation
WO2001026709A2 (en) 1999-09-30 2001-04-19 Therox, Inc. Apparatus and method for blood oxygenation
US6890482B2 (en) 1999-09-30 2005-05-10 Therox, Inc. Apparatus for blood oxygenation
US6596235B2 (en) * 1999-09-30 2003-07-22 Therox, Inc. Method for blood oxygenation
US6759008B1 (en) * 1999-09-30 2004-07-06 Therox, Inc. Apparatus and method for blood oxygenation
US7572374B2 (en) * 2000-04-13 2009-08-11 Transvivo, Inc. Anticoagulant and thrombo-resistant hollow fiber membranes for in-vivo plasmapheresis and ultrafiltration
US6659973B2 (en) * 2001-01-04 2003-12-09 Transvivo, Inc. Apparatus and method for in-vivo plasmapheresis using periodic backflush
US7476210B2 (en) * 2001-01-04 2009-01-13 Transvivo Inc. Apparatus and method for in-vivo plasmapheresis using periodic backflush containing anticoagulant
US6814718B2 (en) 2001-01-09 2004-11-09 Rex Medical, L.P Dialysis catheter
US7011645B2 (en) * 2001-01-09 2006-03-14 Rex Medical, L.P. Dialysis catheter
US8323228B2 (en) 2007-04-12 2012-12-04 Rex Medical L.P. Dialysis catheter
US7077829B2 (en) * 2001-01-09 2006-07-18 Rex Medical, L.P. Dialysis catheter
EP1357920B1 (en) * 2001-02-01 2007-09-05 Hydron Technologies Inc. Compositions and method of tissue superoxygenation
US6613280B2 (en) * 2001-03-20 2003-09-02 Therox, Inc. Disposable cartridge for producing gas-enriched fluids
US6582387B2 (en) * 2001-03-20 2003-06-24 Therox, Inc. System for enriching a bodily fluid with a gas
US7122027B2 (en) * 2001-05-25 2006-10-17 Medtronic, Inc. Implantable medical device with controllable gaseous agent release system
AU2002332450A1 (en) * 2001-08-01 2003-02-17 Eric C. Burckle Artificial pulmonary capillary
US20070160645A1 (en) * 2001-10-25 2007-07-12 Jakob Vinten-Johansen PostConditioning System And Method For The Reduction Of Ischemic-Reperfusion Injury In The Heart And Other Organs
EP1438085B1 (en) 2001-10-25 2008-10-15 Emory University Catheter for modified perfusion
US7280865B2 (en) * 2001-12-20 2007-10-09 Accuray Incorporated Anchored fiducial apparatus and method
US6758836B2 (en) 2002-02-07 2004-07-06 C. R. Bard, Inc. Split tip dialysis catheter
US9955994B2 (en) 2002-08-02 2018-05-01 Flowcardia, Inc. Ultrasound catheter having protective feature against breakage
US8133236B2 (en) 2006-11-07 2012-03-13 Flowcardia, Inc. Ultrasound catheter having protective feature against breakage
US7220233B2 (en) 2003-04-08 2007-05-22 Flowcardia, Inc. Ultrasound catheter devices and methods
US7137963B2 (en) 2002-08-26 2006-11-21 Flowcardia, Inc. Ultrasound catheter for disrupting blood vessel obstructions
US6942677B2 (en) 2003-02-26 2005-09-13 Flowcardia, Inc. Ultrasound catheter apparatus
US7335180B2 (en) 2003-11-24 2008-02-26 Flowcardia, Inc. Steerable ultrasound catheter
US7604608B2 (en) 2003-01-14 2009-10-20 Flowcardia, Inc. Ultrasound catheter and methods for making and using same
US7335334B2 (en) * 2003-01-14 2008-02-26 Medtronic, Inc. Active air removal from an extracorporeal blood circuit
US7204958B2 (en) * 2003-01-14 2007-04-17 Medtronic, Inc. Extracorporeal blood circuit air removal system and method
US7201870B2 (en) * 2003-01-14 2007-04-10 Medtronic, Inc. Active air removal system operating modes of an extracorporeal blood circuit
US7189352B2 (en) * 2003-01-14 2007-03-13 Medtronic, Inc. Extracorporeal blood circuit priming system and method
US7198751B2 (en) * 2003-01-14 2007-04-03 Medtronic, Inc. Disposable, integrated, extracorporeal blood circuit
US7393339B2 (en) 2003-02-21 2008-07-01 C. R. Bard, Inc. Multi-lumen catheter with separate distal tips
US7022099B2 (en) * 2003-03-17 2006-04-04 Cardiovention, Inc. Extracorporeal blood handling system with automatic flow control and methods of use
US20040243095A1 (en) 2003-05-27 2004-12-02 Shekhar Nimkar Methods and apparatus for inserting multi-lumen spit-tip catheters into a blood vessel
WO2005006942A2 (en) * 2003-07-11 2005-01-27 The Brigham And Women's Hospital, Inc. Cardioscopy
US7758510B2 (en) 2003-09-19 2010-07-20 Flowcardia, Inc. Connector for securing ultrasound catheter to transducer
US7455812B2 (en) * 2003-10-16 2008-11-25 Rheoxtech, Llc Method and apparatus for controlled reoxygenation
US8992454B2 (en) 2004-06-09 2015-03-31 Bard Access Systems, Inc. Splitable tip catheter with bioresorbable adhesive
US7540852B2 (en) 2004-08-26 2009-06-02 Flowcardia, Inc. Ultrasound catheter devices and methods
JP4094600B2 (en) * 2004-10-06 2008-06-04 日機装株式会社 Blood purification equipment
US20060084931A1 (en) * 2004-10-19 2006-04-20 Shao-Shih Huang Multi-function medical device
US20080009784A1 (en) * 2004-11-22 2008-01-10 Leedle John D Dialysis catheter
US8118740B2 (en) * 2004-12-20 2012-02-21 Ipventure, Inc. Moisture sensor for skin
AU2005319144A1 (en) * 2004-12-22 2006-06-29 Emory University Therapeutic adjuncts to enhance the organ protective effects of postconditioning
US8221343B2 (en) 2005-01-20 2012-07-17 Flowcardia, Inc. Vibrational catheter devices and methods for making same
US7361188B2 (en) * 2005-04-08 2008-04-22 Exelys, Llc Portable cardiac monitor
WO2006118817A1 (en) * 2005-04-21 2006-11-09 University Of Pittsburgh Of The Commonwealth System Of Higher Education Paracorporeal respiratory assist lung
US8163002B2 (en) * 2005-11-14 2012-04-24 Vascular Devices Llc Self-sealing vascular graft
US9282984B2 (en) 2006-04-05 2016-03-15 Flowcardia, Inc. Therapeutic ultrasound system
US7922757B2 (en) * 2006-10-23 2011-04-12 Rex Medical, L.P. Vascular conduit
AU2007308840C1 (en) 2006-10-25 2014-09-25 Revalesio Corporation Methods of therapeutic treatment of eyes and other human tissues using an oxygen-enriched solution
EP3170401B1 (en) 2006-10-25 2019-06-05 Revalesio Corporation Ionic aqueous fluid composition containing oxygen microbubbles
WO2008115290A2 (en) 2006-10-25 2008-09-25 Revalesio Corporation Methods of wound care and treatment
US8609148B2 (en) 2006-10-25 2013-12-17 Revalesio Corporation Methods of therapeutic treatment of eyes
US8784897B2 (en) 2006-10-25 2014-07-22 Revalesio Corporation Methods of therapeutic treatment of eyes
US8445546B2 (en) 2006-10-25 2013-05-21 Revalesio Corporation Electrokinetically-altered fluids comprising charge-stabilized gas-containing nanostructures
US8784898B2 (en) 2006-10-25 2014-07-22 Revalesio Corporation Methods of wound care and treatment
US8246643B2 (en) 2006-11-07 2012-08-21 Flowcardia, Inc. Ultrasound catheter having improved distal end
EP2164548A4 (en) 2007-06-26 2011-12-07 Avalon Lab Llc Coaxial venal cannula
US20090062735A1 (en) * 2007-08-27 2009-03-05 Bartlett Robert H Introducer for cannula and method
US8333195B2 (en) * 2007-07-18 2012-12-18 Vapotherm, Inc. System and method for delivering a heated and humidified gas
EP2195051B1 (en) 2007-09-14 2019-11-27 Nordson Corporation Cannula reinforcing band and method
US8905023B2 (en) 2007-10-05 2014-12-09 Vapotherm, Inc. Hyperthermic humidification system
US9101711B2 (en) * 2007-10-07 2015-08-11 Chi-Wei Tao Intravascular nano-bubbling oxygenator
CN101918066B (en) 2007-10-17 2013-07-31 巴德阿克塞斯系统股份有限公司 Manufacture of split tip catheters and the split tip catheters
US9745567B2 (en) 2008-04-28 2017-08-29 Revalesio Corporation Compositions and methods for treating multiple sclerosis
US10125359B2 (en) 2007-10-25 2018-11-13 Revalesio Corporation Compositions and methods for treating inflammation
US9523090B2 (en) 2007-10-25 2016-12-20 Revalesio Corporation Compositions and methods for treating inflammation
US8292841B2 (en) 2007-10-26 2012-10-23 C. R. Bard, Inc. Solid-body catheter including lateral distal openings
US8066660B2 (en) 2007-10-26 2011-11-29 C. R. Bard, Inc. Split-tip catheter including lateral distal openings
US8092415B2 (en) 2007-11-01 2012-01-10 C. R. Bard, Inc. Catheter assembly including triple lumen tip
US9579485B2 (en) 2007-11-01 2017-02-28 C. R. Bard, Inc. Catheter assembly including a multi-lumen configuration
JP5901291B2 (en) 2008-05-01 2016-04-06 リバルシオ コーポレイション Compositions and methods for treating digestive disorders
EP2313126A4 (en) * 2008-07-17 2018-03-28 Rheoxtech, LLC Method and apparatus for mitigating acute reoxygenation injury during percutaneous coronary intervention
US8636952B2 (en) 2008-12-04 2014-01-28 Therox, Inc. System for enriching a bodily fluid with a gas having a removable gas-enrichment device with an information recording element
US20100143190A1 (en) * 2008-12-04 2010-06-10 Therox, Inc. System for enriching a bodily fluid with a gas having occlusion detection capabilities
US8246564B2 (en) 2008-12-04 2012-08-21 Therox, Inc. System for enriching a bodily fluid with a gas having automated priming capabilities
US8192384B2 (en) 2008-12-04 2012-06-05 Therox, Inc. System for enriching a bodily fluid with a gas having a dual-function power switch mechanism
US8579266B2 (en) * 2009-01-12 2013-11-12 Jason International, Inc. Microbubble therapy method and generating apparatus
US8322634B2 (en) * 2009-01-12 2012-12-04 Jason International, Inc. Microbubble therapy method and generating apparatus
US8720867B2 (en) * 2009-01-12 2014-05-13 Jason International, Inc. Microbubble therapy method and generating apparatus
US8201811B2 (en) * 2009-01-12 2012-06-19 Jason International, Inc. Microbubble therapy method and generating apparatus
US9060916B2 (en) 2009-01-12 2015-06-23 Jason International, Inc. Microbubble therapy method and generating apparatus
US8815292B2 (en) 2009-04-27 2014-08-26 Revalesio Corporation Compositions and methods for treating insulin resistance and diabetes mellitus
US8226566B2 (en) 2009-06-12 2012-07-24 Flowcardia, Inc. Device and method for vascular re-entry
US8888737B2 (en) 2009-10-20 2014-11-18 Rheoxtech, Llc Method and apparatus for cardiac tissue monitoring and catheter-based perfusion for mitigating acute reoxygenation injury
RS20100326A2 (en) * 2010-03-20 2012-04-30 Uroš BABIĆ Manual device for cardio-circulatory resuscitation
AU2011249856B2 (en) 2010-05-07 2015-11-26 Revalesio Corporation Compositions and methods for enhancing physiological performance and recovery time
US8591450B2 (en) 2010-06-07 2013-11-26 Rex Medical L.P. Dialysis catheter
BR112013003110A2 (en) 2010-08-12 2016-06-28 Revalesio Corp compositions and methods for the treatment of taupathy
US9521990B2 (en) 2011-05-11 2016-12-20 Acist Medical Systems, Inc. Variable-stiffness imaging window and production method thereof
WO2013109269A1 (en) 2012-01-18 2013-07-25 Bard Peripheral Vascular, Inc. Vascular re-entry device
US9545472B2 (en) * 2012-03-02 2017-01-17 Medtronic, Inc. Extracorporeal blood circuit reservoir with angled venous inlet luer port
US10905851B2 (en) 2012-03-23 2021-02-02 Acist Medical Systems, Inc. Catheter sheath and methods thereof
US9919276B2 (en) 2012-05-01 2018-03-20 Therox, Inc. System and method for bubble-free gas-enrichment of a flowing liquid within a conduit
JP6293145B2 (en) 2012-08-02 2018-03-14 バード・ペリフェラル・バスキュラー・インコーポレーテッド Ultrasound catheter system
US9414752B2 (en) 2012-11-09 2016-08-16 Elwha Llc Embolism deflector
USD748252S1 (en) 2013-02-08 2016-01-26 C. R. Bard, Inc. Multi-lumen catheter tip
US9566811B2 (en) 2013-09-20 2017-02-14 Veltek Associates, Inc. Portable cleanroom printing cabinet
US9643439B2 (en) 2013-09-20 2017-05-09 Veltek Associates, Inc. Portable cleanroom printing cabinet
EP3055072B1 (en) 2013-10-11 2023-01-11 3M Innovative Properties Company Nozzle assemblies, systems and related methods
US10035615B2 (en) 2013-10-11 2018-07-31 Veltek Associates, Inc. Method of packaging sterilized products
US10173030B2 (en) 2013-11-15 2019-01-08 Oakwood Healthcare, Inc. Catheter for infusion of a cardiovascular fluid
WO2015095588A1 (en) * 2013-12-19 2015-06-25 Acist Medical Systems, Inc. Catheter sheath system and method
US10258768B2 (en) 2014-07-14 2019-04-16 C. R. Bard, Inc. Apparatuses, systems, and methods for inserting catheters having enhanced stiffening and guiding features
US10596345B2 (en) 2014-12-31 2020-03-24 Vapotherm, Inc. Systems and methods for humidity control
US10398871B2 (en) 2015-03-31 2019-09-03 Vapotherm, Inc. Systems and methods for patient-proximate vapor transfer for respiratory therapy
US10905836B2 (en) 2015-04-02 2021-02-02 Hill-Rom Services Pte. Ltd. Manifold for respiratory device
WO2017084683A1 (en) * 2015-11-20 2017-05-26 Hepa Wash Gmbh Method for extracorporeal lung support
WO2017084682A1 (en) 2015-11-20 2017-05-26 Hepa Wash Gmbh Method for extracorporeal carbon dioxide removal
EP3884853B1 (en) * 2016-05-25 2024-03-13 Zevex, Inc. Sensing system for multiple lumen tubing
AU2017341838A1 (en) 2016-10-14 2019-05-02 Vapotherm, Inc. Systems and methods for high velocity nasal insufflation
US20180140321A1 (en) 2016-11-23 2018-05-24 C. R. Bard, Inc. Catheter With Retractable Sheath And Methods Thereof
US11596726B2 (en) 2016-12-17 2023-03-07 C.R. Bard, Inc. Ultrasound devices for removing clots from catheters and related methods
US10758256B2 (en) 2016-12-22 2020-09-01 C. R. Bard, Inc. Ultrasonic endovascular catheter
US10582983B2 (en) 2017-02-06 2020-03-10 C. R. Bard, Inc. Ultrasonic endovascular catheter with a controllable sheath
IL270771B2 (en) 2017-05-22 2023-12-01 Advitos Gmbh Methods and systems for removing carbon dioxide
JP7082199B2 (en) * 2017-11-28 2022-06-07 セント・ジュード・メディカル,カーディオロジー・ディヴィジョン,インコーポレイテッド Controllable deployable catheter
CN112755288B (en) * 2020-12-21 2022-06-14 山东壹瑞特生物科技有限公司 In-vitro liver support system

Citations (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2474665A (en) * 1946-02-26 1949-06-28 Frank J Guarino Pneumatic blood treating apparatus
US3142296A (en) * 1962-05-31 1964-07-28 Jack W Love Blood oxygenator
US3437450A (en) * 1965-01-04 1969-04-08 James M Greenwood Hyperbaric heart pump oxygenator with hypothermia
US3512517A (en) * 1964-11-30 1970-05-19 Beckman Instruments Inc Polarographic method and apparatus for monitoring blood glucose concentration
US4041180A (en) * 1975-04-08 1977-08-09 Brewing Patents Limited Introducing gases into fermentation liquids
US4317731A (en) * 1978-03-27 1982-03-02 Fmc Corporation Gas absorber
US4406656A (en) * 1981-06-01 1983-09-27 Brack Gillium Hattler Venous catheter having collapsible multi-lumens
US4442843A (en) * 1980-11-17 1984-04-17 Schering, Ag Microbubble precursors and methods for their production and use
US4466804A (en) * 1981-09-25 1984-08-21 Tsunekazu Hino Extracorporeal circulation of blood
US4493692A (en) * 1982-09-29 1985-01-15 Reed Charles C Blood gas concentration control apparatus and method
US4581012A (en) * 1984-12-05 1986-04-08 I-Flow Corporation Multilumen catheter set
US4596210A (en) * 1982-09-04 1986-06-24 Kohlensaurewerke C. G. Rommenholler Gmbh Method and device for dissolving gas, especially carbon dioxide, in liquid fuel and for distributing the fuel in a supersaturated state through the combustion air
US4648865A (en) * 1984-01-12 1987-03-10 Karl Aigner Device for in vivo purification of blood
US4657756A (en) * 1980-11-17 1987-04-14 Schering Aktiengesellschaft Microbubble precursors and apparatus for their production and use
US4664680A (en) * 1986-04-07 1987-05-12 Atec Inc. Method and system for enriching oxygen content of water
US4681119A (en) * 1980-11-17 1987-07-21 Schering Aktiengesellschaft Method of production and use of microbubble precursors
US4769241A (en) * 1986-09-23 1988-09-06 Alpha Therapeutic Corporation Apparatus and process for oxygenation of liquid state dissolved oxygen-carrying formulation
US4828543A (en) * 1986-04-03 1989-05-09 Weiss Paul I Extracorporeal circulation apparatus
US4871450A (en) * 1987-08-20 1989-10-03 Camp Dresser & Mckee, Inc. Water/wastewater treatment apparatus
US4874509A (en) * 1987-04-24 1989-10-17 Donald Bullock Oxidation saturation device
US4973558A (en) * 1988-04-28 1990-11-27 Endotronics, Inc. Method of culturing cells using highly gas saturated media
US5006352A (en) * 1987-02-27 1991-04-09 Mester-Coop Elelmiszeripari Es Ker. Leanyvallalat Process for the production of an oxygenated restorative drink
US5084011A (en) * 1990-01-25 1992-01-28 Grady Daniel J Method for oxygen therapy using hyperbarically oxygenated liquid
US5086620A (en) * 1991-02-14 1992-02-11 Wayne State University Method of microencapsulation of hyperbaric gas
US5135517A (en) * 1990-07-19 1992-08-04 Catheter Research, Inc. Expandable tube-positioning apparatus
US5171216A (en) * 1989-08-28 1992-12-15 Thermedics, Inc. Multi-lumen catheter coupling
US5211546A (en) * 1990-05-29 1993-05-18 Nu-Tech Industries, Inc. Axial flow blood pump with hydrodynamically suspended rotor
US5261875A (en) * 1991-02-14 1993-11-16 Wayne State University Method and apparatus for injection of gas hydrates
US5279565A (en) * 1993-02-03 1994-01-18 Localmed, Inc. Intravascular treatment apparatus and method
US5322500A (en) * 1991-05-09 1994-06-21 Cardio Pulmonary Supplies, Inc. Variable ratio blood-additive solution device and delivery system
US5394732A (en) * 1993-09-10 1995-03-07 Cobe Laboratories, Inc. Method and apparatus for ultrasonic detection of air bubbles
US5407426A (en) * 1991-02-14 1995-04-18 Wayne State University Method and apparatus for delivering oxygen into blood
US5409455A (en) * 1993-07-09 1995-04-25 Scimed Life Systems, Inc. Vascular navigation and visualization assist device
US5509900A (en) * 1992-03-02 1996-04-23 Kirkman; Thomas R. Apparatus and method for retaining a catheter in a blood vessel in a fixed position
US5569180A (en) * 1991-02-14 1996-10-29 Wayne State University Method for delivering a gas-supersaturated fluid to a gas-depleted site and use thereof
US5599296A (en) * 1991-02-14 1997-02-04 Wayne State University Apparatus and method of delivery of gas-supersaturated liquids
US5693017A (en) * 1991-02-14 1997-12-02 Wayne State University Apparatus and method of delivery of gas-supersaturated solutions to a delivery site
US5695717A (en) * 1993-06-18 1997-12-09 Fresenius Ag Gas exchange apparatus
US5709654A (en) * 1990-10-10 1998-01-20 Life Resuscitation Technologies, Inc. Apparatus for cooling living tissue
US5725492A (en) * 1996-03-04 1998-03-10 Cormedics Corp Extracorporeal circulation apparatus and method
US5730698A (en) * 1995-05-09 1998-03-24 Fischell; Robert E. Balloon expandable temporary radioisotope stent system
US5730330A (en) * 1995-06-15 1998-03-24 Reading; Graeme John Liquid dispensing apparatus including visually stimulating syrup display tubes
US5766490A (en) * 1996-01-24 1998-06-16 Life International Products, Inc. Oxygenating apparatus, method for oxygenating water therewith, and applications thereof
US5797876A (en) * 1995-11-27 1998-08-25 Therox, Inc. High pressure perfusion device
US5814222A (en) * 1995-03-31 1998-09-29 Life International Products, Inc. Oxygen enriched liquids, method and apparatus for making, and applications thereof
US5834519A (en) * 1996-10-11 1998-11-10 Wayne State University Stabilized gas-supersaturated emulsions and suspensions
US5843307A (en) * 1994-01-26 1998-12-01 Gie Anjou Recherche Unit for the treatment of water by ozonization, and a corresponding installation for the production of ozonized water
US5849191A (en) * 1993-05-25 1998-12-15 Research And Development Company Bifar (Ru/Ru) Wastewater treatment method, method of suspensions separation and method of saturation of liquid with gas
US5874093A (en) * 1996-11-15 1999-02-23 Eliaz; Isaac Cosmetic composition containing molecular oxygen
US5879282A (en) * 1997-01-21 1999-03-09 Cordis A Johnson And Johnson Company Catheter having an expandable radioactive source
US5893838A (en) * 1997-08-15 1999-04-13 Therox, Inc. System and method for high pressure delivery of gas-supersaturated fluids
US5957899A (en) * 1995-11-27 1999-09-28 Therox, Inc. High pressure transluminal fluid delivery device
US6180059B1 (en) * 1995-06-05 2001-01-30 Therox, Inc. Method for the preparation and delivery of gas-enriched fluids

Family Cites Families (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2827901A (en) 1955-02-15 1958-03-25 George W Jones Means for oxygenating blood
US2876769A (en) 1955-10-11 1959-03-10 Cordova Jose Juan Apparatus for oxygenating, centrifuging and changing the temperature of blood
US2847008A (en) 1955-11-14 1958-08-12 Research Corp Blood handling system for extracorporeal circulation devices
US3795088A (en) * 1972-03-03 1974-03-05 W Esmond Degassing particulate matter and oil filter device
FR2502499B1 (en) * 1981-03-27 1987-01-23 Farcot Jean Christian APPARATUS FOR BLOOD RETROPERFUSION, IN PARTICULAR FOR THE TREATMENT OF INFARCTUS BY INJECTION OF ARTERIAL BLOOD INTO THE CORONARY SINUS
US4540399A (en) 1983-02-01 1985-09-10 Ken Litzie Emergency bypass system
US5730935A (en) * 1984-07-12 1998-03-24 Wayne State University High pressure gas exchanger
US4648384A (en) 1984-11-21 1987-03-10 Schmukler Robert E Retrograde coronary sinus perfusion device and method
US4813951A (en) * 1987-05-20 1989-03-21 Joel Wall Self-actuated implantable pump
JP2736902B2 (en) * 1988-10-11 1998-04-08 テルモ株式会社 Tube body and blood perfusion device
US5061236A (en) * 1990-07-16 1991-10-29 Baxter International Inc. Venous reservoir with improved inlet configuration and integral screen for bubble removal
US5186713A (en) * 1990-11-01 1993-02-16 Baxter International Inc. Extracorporeal blood oxygenation system and method for providing hemoperfusion during transluminal balloon angioplasty procedures
USRE37379E1 (en) * 1991-02-14 2001-09-18 Wayne State University High pressure gas exchanger
US5368555A (en) * 1992-12-29 1994-11-29 Hepatix, Inc. Organ support system
CA2153390A1 (en) * 1993-01-07 1994-07-21 Michael Richard Williams Low pressure contactor
US5407424A (en) * 1993-02-24 1995-04-18 Scimed Life Systems, Inc. Angioplasty perfusion pump
US5413559A (en) * 1993-07-08 1995-05-09 Sirhan; Motasim M. Rapid exchange type over-the-wire catheter
US5505698A (en) * 1993-10-29 1996-04-09 Medtronic, Inc. Cardioplegia catheter with elongated cuff
US5807356A (en) * 1994-01-18 1998-09-15 Vasca, Inc. Catheter with valve
US5466216A (en) * 1994-04-11 1995-11-14 Gish Biomedical, Inc. Antegrade/retrograde cardioplegia method and system
US5597377A (en) * 1994-05-06 1997-01-28 Trustees Of Boston University Coronary sinus reperfusion catheter
US6607698B1 (en) 1997-08-15 2003-08-19 Therox, Inc. Method for generalized extracorporeal support
EP0799406B1 (en) 1994-12-20 2000-02-23 Robert Bosch Gmbh Indicator
US5716318A (en) * 1995-04-14 1998-02-10 The University Of North Carolina At Chapel Hill Method of treating cardiac arrest and apparatus for same
CA2174806A1 (en) * 1995-04-24 1996-10-25 Frank Sever Jr. Method and apparatus for enabling extracorporeal therapeutic treatment of a living patient's entire blood supply during a single uninterrupted time interval
US5843023A (en) * 1995-10-04 1998-12-01 Cecchi; Michael Aspiration needle with side port
US6235007B1 (en) 1995-11-27 2001-05-22 Therox, Inc. Atraumatic fluid delivery devices
US5840067A (en) * 1997-02-28 1998-11-24 Berguer; Ramon Centerflow catheter
FR2761891B1 (en) * 1997-04-14 1999-09-24 Synthelabo FLEXIBLE SURGICAL DRAIN WITH A PLURALITY OF INDIVIDUAL DUCTS
AU7467098A (en) 1997-04-16 1998-11-11 Wayne State University System and method for delivery of gas-supersaturated fluids

Patent Citations (61)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2474665A (en) * 1946-02-26 1949-06-28 Frank J Guarino Pneumatic blood treating apparatus
US3142296A (en) * 1962-05-31 1964-07-28 Jack W Love Blood oxygenator
US3512517A (en) * 1964-11-30 1970-05-19 Beckman Instruments Inc Polarographic method and apparatus for monitoring blood glucose concentration
US3437450A (en) * 1965-01-04 1969-04-08 James M Greenwood Hyperbaric heart pump oxygenator with hypothermia
US4041180A (en) * 1975-04-08 1977-08-09 Brewing Patents Limited Introducing gases into fermentation liquids
US4317731A (en) * 1978-03-27 1982-03-02 Fmc Corporation Gas absorber
US4681119A (en) * 1980-11-17 1987-07-21 Schering Aktiengesellschaft Method of production and use of microbubble precursors
US4442843A (en) * 1980-11-17 1984-04-17 Schering, Ag Microbubble precursors and methods for their production and use
US4657756A (en) * 1980-11-17 1987-04-14 Schering Aktiengesellschaft Microbubble precursors and apparatus for their production and use
US4406656A (en) * 1981-06-01 1983-09-27 Brack Gillium Hattler Venous catheter having collapsible multi-lumens
US4466804A (en) * 1981-09-25 1984-08-21 Tsunekazu Hino Extracorporeal circulation of blood
US4596210A (en) * 1982-09-04 1986-06-24 Kohlensaurewerke C. G. Rommenholler Gmbh Method and device for dissolving gas, especially carbon dioxide, in liquid fuel and for distributing the fuel in a supersaturated state through the combustion air
US4493692A (en) * 1982-09-29 1985-01-15 Reed Charles C Blood gas concentration control apparatus and method
US4648865A (en) * 1984-01-12 1987-03-10 Karl Aigner Device for in vivo purification of blood
US4581012A (en) * 1984-12-05 1986-04-08 I-Flow Corporation Multilumen catheter set
US4828543A (en) * 1986-04-03 1989-05-09 Weiss Paul I Extracorporeal circulation apparatus
US4664680A (en) * 1986-04-07 1987-05-12 Atec Inc. Method and system for enriching oxygen content of water
US4769241A (en) * 1986-09-23 1988-09-06 Alpha Therapeutic Corporation Apparatus and process for oxygenation of liquid state dissolved oxygen-carrying formulation
US4919895A (en) * 1986-09-23 1990-04-24 Alpha Therapeutic Corporation Apparatus for oxygenation of liquid state dissolved oxygen-carrying formulation
US5006352A (en) * 1987-02-27 1991-04-09 Mester-Coop Elelmiszeripari Es Ker. Leanyvallalat Process for the production of an oxygenated restorative drink
US4874509A (en) * 1987-04-24 1989-10-17 Donald Bullock Oxidation saturation device
US4871450A (en) * 1987-08-20 1989-10-03 Camp Dresser & Mckee, Inc. Water/wastewater treatment apparatus
US4973558A (en) * 1988-04-28 1990-11-27 Endotronics, Inc. Method of culturing cells using highly gas saturated media
US5171216A (en) * 1989-08-28 1992-12-15 Thermedics, Inc. Multi-lumen catheter coupling
US5084011A (en) * 1990-01-25 1992-01-28 Grady Daniel J Method for oxygen therapy using hyperbarically oxygenated liquid
US5211546A (en) * 1990-05-29 1993-05-18 Nu-Tech Industries, Inc. Axial flow blood pump with hydrodynamically suspended rotor
US5135517A (en) * 1990-07-19 1992-08-04 Catheter Research, Inc. Expandable tube-positioning apparatus
US5709654A (en) * 1990-10-10 1998-01-20 Life Resuscitation Technologies, Inc. Apparatus for cooling living tissue
US5752929A (en) * 1990-10-10 1998-05-19 Life Resuscitation Technologies, Inc. Method of preserving organs other than the brain
US5261875A (en) * 1991-02-14 1993-11-16 Wayne State University Method and apparatus for injection of gas hydrates
US5693017A (en) * 1991-02-14 1997-12-02 Wayne State University Apparatus and method of delivery of gas-supersaturated solutions to a delivery site
US5797874A (en) * 1991-02-14 1998-08-25 Wayne State University Method of delivery of gas-supersaturated liquids
US5407426A (en) * 1991-02-14 1995-04-18 Wayne State University Method and apparatus for delivering oxygen into blood
US5086620A (en) * 1991-02-14 1992-02-11 Wayne State University Method of microencapsulation of hyperbaric gas
US5735934A (en) * 1991-02-14 1998-04-07 Wayne State University Method for delivering a gas-supersaturated fluid to a gas-depleted site and use thereof
US5569180A (en) * 1991-02-14 1996-10-29 Wayne State University Method for delivering a gas-supersaturated fluid to a gas-depleted site and use thereof
US5599296A (en) * 1991-02-14 1997-02-04 Wayne State University Apparatus and method of delivery of gas-supersaturated liquids
US5322500A (en) * 1991-05-09 1994-06-21 Cardio Pulmonary Supplies, Inc. Variable ratio blood-additive solution device and delivery system
US5509900A (en) * 1992-03-02 1996-04-23 Kirkman; Thomas R. Apparatus and method for retaining a catheter in a blood vessel in a fixed position
US5279565A (en) * 1993-02-03 1994-01-18 Localmed, Inc. Intravascular treatment apparatus and method
US5849191A (en) * 1993-05-25 1998-12-15 Research And Development Company Bifar (Ru/Ru) Wastewater treatment method, method of suspensions separation and method of saturation of liquid with gas
US5695717A (en) * 1993-06-18 1997-12-09 Fresenius Ag Gas exchange apparatus
US5409455A (en) * 1993-07-09 1995-04-25 Scimed Life Systems, Inc. Vascular navigation and visualization assist device
US5394732A (en) * 1993-09-10 1995-03-07 Cobe Laboratories, Inc. Method and apparatus for ultrasonic detection of air bubbles
US5843307A (en) * 1994-01-26 1998-12-01 Gie Anjou Recherche Unit for the treatment of water by ozonization, and a corresponding installation for the production of ozonized water
US5814222A (en) * 1995-03-31 1998-09-29 Life International Products, Inc. Oxygen enriched liquids, method and apparatus for making, and applications thereof
US5885467A (en) * 1995-05-01 1999-03-23 Life International Products, Inc. Method and apparatus for making oxygen enriched liquids
US5730698A (en) * 1995-05-09 1998-03-24 Fischell; Robert E. Balloon expandable temporary radioisotope stent system
US6180059B1 (en) * 1995-06-05 2001-01-30 Therox, Inc. Method for the preparation and delivery of gas-enriched fluids
US5730330A (en) * 1995-06-15 1998-03-24 Reading; Graeme John Liquid dispensing apparatus including visually stimulating syrup display tubes
US5797876A (en) * 1995-11-27 1998-08-25 Therox, Inc. High pressure perfusion device
US5976119A (en) * 1995-11-27 1999-11-02 Wayne State University High pressure perfusion device
US5957899A (en) * 1995-11-27 1999-09-28 Therox, Inc. High pressure transluminal fluid delivery device
US5766490A (en) * 1996-01-24 1998-06-16 Life International Products, Inc. Oxygenating apparatus, method for oxygenating water therewith, and applications thereof
US5725492A (en) * 1996-03-04 1998-03-10 Cormedics Corp Extracorporeal circulation apparatus and method
US5922305A (en) * 1996-10-11 1999-07-13 Wayne State University Methods of treating tissues with oxygen-supersaturated emulsions
US5958377A (en) * 1996-10-11 1999-09-28 Wayne State University Methods of delivering gases to gas-depleted environments
US5834519A (en) * 1996-10-11 1998-11-10 Wayne State University Stabilized gas-supersaturated emulsions and suspensions
US5874093A (en) * 1996-11-15 1999-02-23 Eliaz; Isaac Cosmetic composition containing molecular oxygen
US5879282A (en) * 1997-01-21 1999-03-09 Cordis A Johnson And Johnson Company Catheter having an expandable radioactive source
US5893838A (en) * 1997-08-15 1999-04-13 Therox, Inc. System and method for high pressure delivery of gas-supersaturated fluids

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6899847B2 (en) 1999-09-30 2005-05-31 Therox, Inc. Apparatus for blood oxygenation
US6849235B2 (en) 1999-09-30 2005-02-01 Therox, Inc. Method of forming gas-enriched fluid
WO2008042721A3 (en) * 2006-09-29 2008-05-15 Zevex Inc Method and apparatus for detecting air bubbles
WO2008042721A2 (en) * 2006-09-29 2008-04-10 Zevex, Inc. Method and apparatus for detecting air bubbles
US20080103445A1 (en) * 2006-09-29 2008-05-01 Blaine David H Method and Apparatus for Detecting Air Bubbles
US7726174B2 (en) 2006-10-24 2010-06-01 Zevex, Inc. Universal air bubble detector
US20080134750A1 (en) * 2006-10-24 2008-06-12 Riley Timothy A Universal air bubble detector
US20090293588A1 (en) * 2006-10-24 2009-12-03 Riley Timothy A Universal air bubble detector
US20080098798A1 (en) * 2006-10-24 2008-05-01 Riley Timothy A Method for making and using an air bubble detector
US7805978B2 (en) 2006-10-24 2010-10-05 Zevex, Inc. Method for making and using an air bubble detector
US7818992B2 (en) 2006-10-24 2010-10-26 Zevex, Inc. Universal air bubble detector
US8225639B2 (en) 2006-10-24 2012-07-24 Zevex, Inc. Universal air bubble detector
US8910370B2 (en) 2006-10-24 2014-12-16 Zevex, Inc. Method of making a universal bubble detector
US7987722B2 (en) 2007-08-24 2011-08-02 Zevex, Inc. Ultrasonic air and fluid detector
US8303613B2 (en) 2007-12-07 2012-11-06 Zevex, Inc. Ultrasonic instrument using langevin type transducers to create transverse motion
US8539812B2 (en) 2009-02-06 2013-09-24 Zevek, Inc. Air bubble detector
US8646309B2 (en) 2009-02-06 2014-02-11 Zevek, Inc. Air bubble detector
US8739601B2 (en) 2009-02-06 2014-06-03 Zevex, Inc. Air bubble detector

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