Medical apparatus for the preparation and delivery of gas-enriched fluids

IS 2 296 396 T3

DESCRIPTION

Medical device for the preparation and administration of gas-enriched fluids.

Field of application of the invention

The present invention relates generally to an apparatus for the preparation and administration of gas-enriched fluids to places where gas has been depleted, and more particularly, to a system for the preparation and administration of physiological solutions for the treatment of conditions such as tissue ischemia and post-ischemic tissues, including but not limited to, a catheter for delivering oxygen-enriched blood to specific locations within a patient's body.

Background of the invention

Oxygen is a crucial nutrient element for human cells. Deterioration of cells could result from oxygen deprivation even for short periods of time, which could lead to organ dysfunction or failure. For example, victims of heart attacks and strokes experience blood flow obstructions or diversions that prevent oxygen from being delivered to vital tissue cells. Without oxygen, the heart and brain progressively deteriorate. In severe cases, death occurs as a consequence of the complete failure of an organ. Less serious cases typically involve high hospital costs, specialized treatments, and lengthy rehabilitation.

Oxygen levels in the blood could be described as a function of the partial pressure of dissolved oxygen in the blood (pO₂). Typically, for arterial blood, normal blood oxygen levels (ie, normoxia or normoxemia) are in the range of 90 to 110 mm Hg (12 to 15 kPA). Hypoxemic blood (ie, hypoxemia) is arterial blood with a pO2 less than 90 mm HG (12 kPA). Hyperoxic blood (i.e., hyperoxemia or hyperoxia) is arterial blood with a pO₂ greater than 400 mm HG (534 kPA) (see Cason et al. (1992), Effects of elevated arterial oxygen tension on function, blood circulation distribution, and metabolism in ischemic myocardium, Circulation, Volume 85, No. 2, pages 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, Volume 134, N ° 3, pages 544-550. Hyperbaric blood is arterial blood with a pO2 greater than 760 mm Hg (101 kPA). Venous blood typically has a pO2 level less than 90 mm Hg (12 kPA). In the average adult, for example, normal venous blood oxygen levels generally range from 40 mm Hg to 70 mm Hg (5 to 9 kPA).

Blood oxygen levels could also be defined based on hemoglobin saturation levels. For normal arterial blood, the hemoglobin saturation is approximately 97% and varies only slightly when pO2 levels increase. For normal venous blood, the hemoglobin saturation is approximately 75%.

In patients suffering 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.

Treatment of acute myocardial infarction or myocardial ischemia often involves performing angioplasty or stenting of the vessels to compress, dislodge, or otherwise treat the occlusion (or occlusions) within the vessel walls. For example, a successful angioplasty increases the size of the vessel opening to allow increased blood circulation.

Even with successful treatment of occluded vessels, there may still be a risk of tissue injury. During transluminal percutaneous coronary angioplasty (PTCA), the balloon inflation time is limited by the patient's tolerance to ischemia caused by temporary blockage of blood flow through a vessel during balloon inflation. Revascularization damage could also result, for example, due to slow coronary recirculation or lack of recirculation after angioplasty.

For some patients, angioplasty procedures are not an attractive option for treating vessel obstruction. These patients are at increased risk of ischemia for reasons such as poor left ventricular function, type and location of injury, or the amount of myocardium that is at risk. Therefore, the treatment options for such patients include more invasive procedures such as coronary artery bypass grafting.

To reduce the risk of tissue injury typically associated with acute myocardial infarction and myocardial ischemia treatments, it is usually desirable to administer oxygenated blood or oxygen-enriched fluids to the tissues at risk. Damage to tissue is minimized or prevented by diffusion of dissolved oxygen from blood or fluids to tissue and / or perfusion of blood which removes metabolites and provides other chemical nutrients.

In some cases, the desired treatment of acute myocardial infarction and myocardial ischemia includes infusion of oxygenated blood or oxygen-enriched fluids. During PTCA, for example, you could

ES 2 296 396 T3 increase the tolerated balloon insufflation time by concurrent introduction of oxygenated blood into the patient's coronary artery. Increased oxygen levels in the blood could also cause the normally pre-fused heart tissue of the left ventricle to hypercontract to further increase blood circulation through the vessels of the treated coronary artery.

The infusion of oxygenated blood or oxygen-enriched fluids could also be continued after completion of PTCA treatment or other procedures (eg surgery) where a "stun" of cardiac tissue has occurred with corresponding compromise of myocardial function. In some cases, continued infusion could accelerate reversal of ischemia and facilitate recovery of myocardial function.

Conventional methods for the administration of oxygenated blood or oxygen-enriched fluids involve the use of blood oxygenators. Such procedures generally involve drawing blood from a patient, circulating it through an oxygenator to increase the oxygen concentration in the blood, and then administering the blood back to the patient. An example of a commercially available blood oxygenator is the Maxima blood oxygenator manufactured by Medtronic, Inc., Minneapolis, Minnesota.

However, there are drawbacks to using a conventional oxygenator in an extracorporeal circuit to oxygenate blood. Such systems are typically expensive, complex, and difficult to operate. An infusion expert is often required to set up and monitor the system.

Conventional oxygenator systems also typically have a large priming volume, that is, the total volume of blood contained within the oxygenator, the tubes and other components of the system, and associated devices. It is not uncommon in a typical case of an adult patient that the oxygenation system contains more than one to two liters of blood. Such large priming volumes are not desirable for many reasons. For example, in some blood transfusion cases, it may be necessary to compensate for blood temporarily lost to the oxygenation system due to its large priming volume. Heaters must often be used to keep the temperature of the blood at an acceptable level as it circulates through the extracorporeal circuit. Also, conventional oxygenator systems are relatively difficult to connect and disconnect. For example, if the oxygenator is turned off, large stagnant amounts of blood could clot in the oxygenator.

Additionally, with extracorporeal circuits that include conventional blood oxygenators there is a relatively high risk of inflammatory reaction of cells and blood clotting due to the relatively slow blood flow rates and the large surface area of ​​contact with the blood. A blood contact surface area of ​​approximately 1-2 m² and flow rates of about 3 cm / s are not uncommon with conventional oxygenator systems. Thus, a relatively aggressive anticoagulation therapy, such as heparinization, is usually required as an adjunct to the use of an oxygenator.

Perhaps one of the biggest drawbacks to using conventional blood oxygenation systems is that the maximum partial pressure of oxygen (pO₂) that can be imparted to the blood with commercially available oxygenators is approximately 500 mm Hg. Therefore, with these conventional oxygenators, blood pO2 levels close to or greater than 760 mm Hg cannot be achieved.

Some experimental studies for the treatment of myocardial infarction have involved the use of hyperbaric oxygen therapy. See, for example, Shandling et al. (1997), Hyperbaric oxygen and thrombolysis in myocardial infarction; The “HOT MI” pilot study, American Heart Journal, Volume 134, No. 3, pages 544550. These studies have generally involved the placement of patients in chambers of pure oxygen pressurized up to 2 atmospheres, resulting in generalized oxygenation of the patient's blood to a pO2 level of approximately 1,200 mm Hg. However, the use of hyperbaric oxygen therapy after coronary artery repermeabilization in the setting of an acute myocardial infarction is not practical. It is difficult to monitor critically ill patients in a hyperbaric oxygen chamber. Many patients become claustrophobic. Injury to the ear could occur. Furthermore, treatment times greater than 30 minutes cannot be administered without affecting pulmonary oxygen toxicity.

For these reasons, the treatment of regional organ ischemia has not evolved from a clinical point of view. Therefore, there remains a need for a simple and convenient system to administer oxygen-enriched blood and other fluids to patients for localized prevention of ischemia and treatment of post-ischemic tissue and organs.

Document US 3 512 517 describes an apparatus for monitoring blood glucose concentration comprising a catheter and a pump for drawing sampled blood from the vein of a patient.

US 5 211 627 describes an aerated liquid infusion catheter comprising an air lumen and a liquid lumen joined by means of a hole. Accordingly, the air discharged into the air gap can be mixed with the liquid delivered to the fluid within the light.

Document WO 99/08733 describes an apparatus for increasing the concentration of gas in blood comprising a blood pump for drawing blood, a means for the administration of fluid supersaturated in oxygen, and a chamber as a combining means for combining blood. with the fluid supersaturated with oxygen.

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Document US 5 394 732 describes an apparatus for the ultrasonic detection of air bubbles having a transmitter for transmitting a signal through the fluid and a receiver for receiving the transmitted signal. The presence of bubbles is determined based on a comparison between the expected attenuation and the received attenuation of the received signal.

WO 96/17565 describes an apparatus for the administration of a gas such as an oxygen solution into a coronary artery comprising a high pressure tubular housing defining a lumen.

The object of this invention is to provide an apparatus for the preparation of a fluid enriched in a gas to be administered to a patient, in which the priming volume is minimized.

This object is fulfilled by an apparatus having the characteristics described in claim 1. Preferred embodiments are defined in the dependent claims.

Summary of the invention

The present invention could solve one or more of the problems discussed above. Certain embodiments of the present invention are described below by way of example. It should be understood that these aspects are presented simply to provide the reader with a brief summary of certain embodiments that the invention might take, and that these aspects are not limiting. Indeed, the invention could encompass a variety of aspects that may not be specified hereinafter, but are within the scope of the claims.

In one embodiment of the present invention, a system is provided for the preparation and administration of a fluid enriched in a gas. In applications involving the prevention of ischemia or the treatment of ischemic tissues, the system could be used for the preparation and administration of an oxygen-enriched fluid including blood to a specific location within the body of a patient. The system could include a circuit to oxygenate or enrich blood, for example by increasing the level of dissolved oxygen in the blood. The system includes an apparatus that combines a fluid supersaturated in gas with blood to form a fluid enriched in gas, advantageously for regional or localized administration. The gas supersaturated fluid could include an oxygen supersaturated physiological fluid, and the blood to be enriched is drawn from the patient.

The system provided further includes assemblies for supplying controlled flows or feeds of the gas-supersaturated fluid and blood. The system could include an elongated, generally tubular assembly that includes a central lumen and at least one end that can be placed inside the body of a patient close to an area of ​​tissue to be treated, the end of which includes an exit port for the fluid. enriched in gas. The system could include a catheter that defines a fluid path, including a proximal portion intended to engage for supplies of supersaturated fluid in gas and blood, and a distal portion that defines an insertable fluid path. removably within the body of a patient, to infuse the gas-enriched fluid at predetermined locations.

The proximal part of the catheter is adapted to be coupled to a supply of fluid supersaturated in gas, and includes a closed pump circuit through which blood drawn from a blood intake flows. The blood inlet comprises a porous lateral segment or an axial sleeve that defines the inlet into an annular conduit that serves as a transition into a lumen in fluid communication with the closed pump circuit. The intake is arranged along the insertable - removable - catheter portion within the patient's body. Upon insertion of the catheter through an access or opening, for example, an introducer sheath, and after placement within the patient's body, for example, by placing the tip at or near the coronary ostium, the intake of blood is found distal of the access sheath in order to allow the patient's blood to pass through and along the fluid path defined by the blood intake, annular conduit, pump light and closed circuit prior to combining with the gas-supersaturated fluid delivered to the patient via the central catheter lumen and discharge port.

The invention could be used in a method for the preparation and administration of a fluid enriched in a gas. In applications involving the prevention of ischemia or the treatment of ischemic tissues, the method could 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 physiological liquid in which oxygen is dissolved at normalized concentrations at standard temperature and pressure (hereinafter STP), which equal or exceed the volume of the solvent. Examples of solvents that could be used include saline solutions, lactated Ringer's solution, and other water-based physiological solutions.

Furthermore, the invention could be used in a method of delivering an oxygen-enriched fluid to a specific area within the body of a patient. The method comprises raising the pO2 level of the fluid to be delivered to the patient. When the fluid to be infused includes blood, the method could include the step of controlling or providing controlled amounts of the blood and the oxygen supersaturated fluid that are combined to produce an oxygen-enriched fluid for delivery to a specific predetermined area. Blood pO2 levels could be maintained, adjusted, or otherwise controlled by controlling flow rates or providing controlled amounts of the blood and / or fluid supersaturated in oxygen. Thus, a blood and gas control method is provided.

IS 2 296 396 T3

Additionally, administration of the gas-enriched fluid occurs without the formation of clinically significant bubbles. To help minimize or eliminate clinically significant bubble formation, blood contact surfaces are exposed or coated with blood proteins for some short interval of time, usually at least several minutes, before beginning the infusion of supersaturated fluid into oxygen. Also, blood contact surfaces are exposed or pre-moistened with liquids, eg saline, ethanol, and benzalkonium heparin, prior to use. Fluid contact surfaces also do not include any substances that promote such bubble formation, eg, hydrophobic surfaces that are difficult to wet, Teflon, Teflon compound coatings, silicone oils, etc. Hydrophilic fluid contact surfaces are typically useful.

The embodiments could be used in conjunction with angiographic or guiding catheters, arterial wraps, and / or other devices used in angioplasty and other cardiovascular surgical procedures. The system could be used in applications involving one or more vascular openings, that is, in either of the two contralateral or ipsilateral procedures.

In contralateral procedures, blood is drawn from the patient at a first location, eg, the left femoral artery. The blood is enriched and then returned to the patient at a second location close to the tissue to be treated. Blood enrichment occurs when blood pumped through the extracorporeal loop or circuit combines with the gas-supersaturated fluid to form the gas-enriched fluid to be delivered. The catheter includes 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 can be removably inserted into the body of a patient 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 can exit. Additionally, the distal portion of the catheter could be adapted with a tip portion shaped to promote insertion of the device, such as through the same sheath used for surgical procedures such as angioplasty, to specific predetermined locations within a patient's body. . Examples of tip part shapes that could be used include any of the clinically accepted standard configurations used with devices such as guiding catheters to provide access to and clamping on locations such as the coronary ostium. In accordance with the foregoing, the method could further include the step of locating the distal end portion of the catheter that includes the fluid outlet port at a predetermined location within the body of a patient near the tissue to be treated.

In ipsilateral procedures, the system could be used in conjunction with one or more of any of a number of standard size clinically accepted guiding suitable sheaths and / or catheters. The system, for example, could comprise a catheter, a catheter and guiding catheter, or a catheter and sheath, for use within a guiding catheter or introducer sheath used for the primary surgical procedure. In accordance with this embodiment of the present invention, blood is drawn between the catheter assemblies and the guiding catheter or sheath of the present invention, between the catheter assembly of the present invention and the guiding catheter or introducer sheath used for delivery. main interventional procedure, or the annular space between the guiding catheter and the introducer sheath.

As described herein, the preferred supersaturated gas fluid for use in accordance with the present invention is an oxygen supersaturated fluid. However, other fluids could be used depending on the circumstances involved in a particular desired application, such as, for example, supersaturated fluids in which one or more gases such as helium, carbon dioxide and air are dissolved. The oxygen supersaturated fluid could include a normalized volume of dissolved oxygen at standard pressure and temperature of between about 1.7 MPa and about 34.5 MPa (about 250 psi and about 5,000 psi). The exact pressure could vary depending on the circumstances involved in a particular application. In addition, the supplied supersaturated oxygen fluid could be a sterile fluid that does not include gas, bubble or surface nucleation sites where clinically significant bubbles could form.

The catheter system of the present invention has typically been sized according to the circumstances involved in a particular application. In general, the dimensions of the various system components will be on the order of the dimensions of clinically accepted cardiovascular surgical devices. Usually, the extracorporeal closed circuit of the present invention has a total length of less than four meters. Thus, for example, when the system supports blood flow rates between 100 ml / min and 175 ml / min., The priming volume would be approximately 35 ml.

Brief description of the drawings

Additional objects and advantages of the present invention will become apparent upon reading the following detailed description and upon reference to the accompanying drawings, in which:

Figure 1 is a schematic diagram of an exemplary embodiment of a catheter system in accordance with the present invention used in a contralateral surgical procedure.

Figure 2 is a cross-sectional view of an exemplary embodiment of a catheter system including an angled blood flow path in accordance with the present invention.

IS 2 296 396 T3

Figure 3 is a cross-sectional view of part of an alternate exemplary embodiment of a catheter system that includes an angled blood flow path in accordance with the present invention.

Figure 4 is a cross-sectional view of another exemplary embodiment of a catheter system that includes a straight blood flow path in accordance with the present invention.

Figure 4A is a cross-sectional view taken along line AA of Figure 4 of the exemplary embodiment of the catheter system including a straight blood flow path shown in accordance with the present invention.

Figure 5 is a perspective view of part of an exemplary embodiment of a catheter system including an exemplary discharge of oxygen supersaturated fluid in accordance with the present invention.

Figure 5A is a cross-sectional view taken along line AA of Figure 5 of part of the exemplary embodiment of a catheter system including an exemplary discharge of supersaturated oxygen fluid in accordance with the present invention.

Figure 5B is a view of the exemplary oxygen supersaturated fluid discharge shown in Figure 5 in accordance with the present invention.

Figure 6 is a cross-sectional view of part of an exemplary embodiment of a catheter system that includes an integrated blood intake introducer sheath.

Figure 7 is a schematic diagram of an exemplary embodiment of a catheter system for use in an ipsilateral surgical procedure.

Figure 8 is a cross-sectional view of part of an exemplary guiding catheter including an inner liner used with an exemplary embodiment of a catheter system in accordance with the present invention.

Figure 8A is a cross-sectional view of the exemplary guiding catheter shown in Figure 8, without the liner, in accordance with the present invention.

Figure 9 is a cross-sectional view of part of an exemplary catheter system including an integral blood collection device comprising a porous lateral blood intake in accordance with the present invention.

Figure 10 is a cross-sectional view of part of an exemplary catheter system including an integral blood collection device comprising an axial blood intake in accordance with the present invention.

Figure 10A is a cross-sectional view on line AA of Figure 10 of part of an exemplary catheter system in accordance with the present invention.

Figure 11 is a view of part of an alternative exemplary catheter system including an integral blood collection device comprising a porous lateral blood intake in accordance with the present invention.

Figure 11A is a cross-sectional view taken along line AA of Figure 11 of part of an alternative exemplary catheter system including an integral extraction device comprising a porous lateral blood intake in accordance with the present invention.

Figure 11B is a cross-sectional view along line BB of Figure 11 of part of an alternative exemplary catheter system including an integral blood collection device comprising a porous side intake in accordance with the present invention.

Figure 11C is a cross-sectional view along line CC of Figure 11 of part of an alternative exemplary catheter system including an integral blood collection device comprising a porous side intake in accordance with the present invention.

Figure 11D is a cross-sectional view along line DD of Figure 11 of part of an alternative exemplary catheter system including an integral blood collection device comprising a porous side intake in accordance with the present invention.

Figure 12 is a cross-sectional view of an exemplary catheter tip configuration in accordance with the present invention.

Figure 12A is a cross-sectional view along line AA of Figure 12 of an exemplary catheter tip configuration in accordance with the present invention.

Figure 12B is a cross-sectional view along line BB of Figure 12 of an exemplary catheter tip configuration in accordance with the present invention.

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Figure 13 is a cross-sectional view of an alternative exemplary catheter tip configuration in accordance with the present invention.

Figure 13A is a cross-sectional view along line AA of Figure 13 of an alternative exemplary catheter tip configuration in accordance with the present invention.

Figure 13B is a cross-sectional view along line BB of Figure 13 of an alternative exemplary catheter tip configuration in accordance with the present invention.

Figure 14 is a cross-sectional view of an alternative exemplary catheter tip configuration in accordance with the present invention.

Figure 14A is a cross-sectional view of a further alternative exemplary catheter tip configuration in accordance with the present invention.

Figure 15 is an isometric view of an example bubble detector-transducer in accordance with the present invention. Figure 15A is a partially exploded view of a portion of the bubble detector-transducer shown in Figure 15.

The present invention could be susceptible to various modifications and alternative embodiments. Specific embodiments of the present invention have been presented by way of example in the drawings and are described in detail herein. However, it will be understood that the description specified herein of specific embodiments is not intended to limit the present invention to the particular forms described. Rather, it is intended to cover all modifications, alternatives, and equivalents that fall within the scope of the invention as defined by the appended claims.

Detailed description of specific realizations

The following description illustrates embodiments of the present invention. For clarity of discussion, not all features of an actual implementation of the present invention have been described in this specification. It should be noted that, in connection with the development of any actual embodiment of the present invention, many decisions must be made for a specific application in order to achieve specific objectives, which could be vary from application to application. Additionally, it should be noted that any such development attempt could be complicated and time consuming, but it will still be a matter of course for those skilled in the art to benefit from this disclosure.

For clarity and convenience, the various embodiments are described herein in the context of interventional cardiovascular applications generally related to acute or transient ischemia or post-ischemic tissues. However, the present invention could be useful in other medical applications as well, such as cancer therapy (for example the administration of oxygen-enriched fluids directly to poorly vascularized tumors during irradiation or chemotherapy treatments), neurovascular applications (for example, the treatment of stroke and brain trauma patients), lung support in patients with trauma and lung diseases, and wound care management.

Also, while the present invention could be used to increase oxygen levels, for example, in venous and arterial blood, in blood substitutes, for example, perfluorocarbons, and in combinations thereof, for clarity and convenience is referred to herein only to arterial blood.

Furthermore, the present invention could also be used in connection with pharmaceutical fluid infusion therapies. Examples of pharmaceutical fluids used in cardiovascular and neurological surgical procedures that could be infused by the present invention include, but are not limited to, vasodilators (eg, nitroglycerin and nitroprusside), thrombocyte activators (eg, ReoPro and Orbofiban). , thrombolytics (for example, tissue plasminogen activators (hereinafter t-PA), streptokinase and urokinase), antiarrhythmics (for example, lidocaine, procainamide), beta-blockers (eg esmolol, inderal), calcium channel blockers (eg diltiazem, verapamil), magnesium, isotropic agents (eg epinephrine, dopamine), perfluorocarbons (eg fluosol), crystalloids (eg , normal saline, compound sodium lactate solutions), colloids (albumin, sepan), blood products (packed red blood cells, thrombocytes, whole blood), Na + lH + exchange inhibitors, antioxidants, diuretics (eg, mannitol), anticonvulsant drugs, (eg, phenobarbital, valium), and neuroprotectors (eg, lubeluzole).

Turning now to the drawings, a system has been provided in which blood is combined with a fluid supersaturated in oxygen to form an oxygen-enriched fluid that could be delivered to a particular predetermined area within the body of a patient for the treatment of conditions such as tissue ischemia and post-ischemic tissues. As shown in Figure 1, one embodiment of said system 10 includes a blood collection device 12 comprising a continuous fluid flow path between a vascular access point 14 of a patient's body and a pump 16. Selection The vascular access point is typically performed by a physician or patient caregiver and is dependent on the circumstances of the particular application concerned. The particular vascular access point in Figure 1 is the left femoral artery. The 16 blood pump

ES 2 296 396 T3 could be one of many commercially available and clinically approved blood pumps suitable for use with human patients. An example of such a pump is the Model 6501 RFL3.5 Pernco peristaltic pump sold by Pernco Medical, Cleveland, Ohio.

Pump 16 draws blood from the patient and provides a blood feed via tubing 18 to inlet 20 of catheter 22. Blood flow characteristics will depend on the circumstances of the particular application concerned. Typically, the blood supply to the blood intake 20 of catheter 22 will be a controlled flow defined by flow parameters selected by the caregiver. Factors influencing the determination of blood circulation characteristics could include one or more of the many clinical parameters or variables of the blood to be delivered to the catheter or of the oxygen-enriched fluid to be administered to the patient, for For example the dimensions of the patient, the percentage of total circulation to provide, hemolysis, hemodilution. pO2, pulsatility, mass flow rate, volume flow rate, temperature, hemoglobin concentration and pH.

System 10 could include one or more gas bubble detectors, at least one of which is capable of detecting the presence of microbubbles, that is, bubbles with a diameter of about 7 to 10 microns to about 200 microns (see, for example, Figure 12). Additionally, the system could include one or more macro bubble detectors to detect larger bubbles, such as bubbles with diameters of 1 millimeter or greater. Such macro-bubble detectors could comprise any suitable commercially available detector, such as an outer, tube-mounted bubble detector that includes two transducers that measure the attenuation of a sound pulse traveling from one side of the tube to the other. One such suitable detector is sold by Transonic Inc. of New York. Microbubble and macrobubble detectors provide the clinician or caregiver with a warning of potentially clinically significant bubble generation. The system 10 could also include various conventional elements, such as flow meters (which could also serve a dual role as a macro bubble detector), or other clinical parameter monitoring devices; access holes that allow the extraction of fluids; filters or other safety devices that help ensure sterility; or other devices that in general could help to control the circulation of one or more of the fluids contained in the system 10. Advantageously, any of said devices could be located within the system and used in order to avoid the formation of clinically significant bubbles. within the fluid circulation paths.

Catheter 22 includes a proximal part 24 and a distal part 26, the distal part of which can be removably inserted into the body of a patient through an opening or vascular access 36. The proximal part includes a blood inlet 20. Blood inlet 20 and tubing 18 could be releasably coupled, for example, with a clinically approved fluid connection apparatus such as a catheter-type cone, to allow catheter 22 to receive delivered blood through the tube. Tubing 18. Catheter 22 includes a lumen defining a continuous blood flow path from blood intake 20 to a fluid discharge port proximate distal tip 28 of catheter 22.

Proximal portion 24 of catheter 22 also includes a fluid intake port 30 for engagement with a supply 32 of fluid supersaturated in oxygen. Orifice 30 is in fluid communication with feed 32 and with pipe 34. Tubing 34 comprises one or more capillary members or other generally tubular elongated members including central lumens, either alone or in a group, each of which defines a continuous fluid flow path between orifice 30 and the flow path. blood flow from catheter 22.

The oxygen supersaturated fluid is usually delivered to port 30 in accordance with parameters specified and selected by the caregiver for the desired clinical indication. The circulation of fluid supersaturated in oxygen is generally stable and continuous, although variable or intermittent circulations could be used. Flow rates could range from about 0.1 cc / min. up to about 40 cc / min, particularly advantageous flow rates could be between about 2 cc / min. and 12 cc / min. Oxygen concentrations could range from a physiological solution of approximately 0.5 cc of O₂ per cc to a physiological solution of about 3 cc of O2 per cc, although particularly advantageous concentrations could be a physiological solution of about 1 cc of O2 per cc. The oxygen-supersaturated fluid is provided at temperatures such that when the fluid combines with the blood to form the oxygen-enriched fluid to be infused, the oxygen-enriched fluid is approximately 37 ° C, that is, the operation of the system does not significantly affect the temperature of the patient's blood.

Figure 2 presents an embodiment in which the catheter part 40 comprises a section of the catheter in which the circulations of blood and fluid supersaturated in oxygen are combined. Catheter portion 40 comprises the proximal end of an elongated tubular member 48, including a generally centrally disposed fluid return lumen 52, installed within a housing 42 that includes a blood intake lumen 44. Lumen 44 defines a continuous fluid flow path between catheter blood intake port 46 and proximal end 50 of fluid return lumen 52. The distal portion of the member 48 (not shown) can be removably inserted into the body of a patient, and includes the exit port through which fluid travels into the fluid return lumen 52. it is administered to a site within a patient's body.

Housing 42 typically comprises a biocompatible molded polymer material. The exact size and shape of housing 42 could vary depending on the circumstances of a particular application.

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Figure 2, by way of example, presents a generally Y-shaped configuration. Tubular member 48 could be integrally formed with housing 42. However, tubular member 48 could comprise a clinically approved polymer tube. The proximal end of member 48 is securely attached within housing 42. Typically, attachment of housing 42 and member 48 is by solvent or adhesive bonding or by overmolding or insertion.

The diameter and shape of the lumen 44 could also vary depending on the circumstances of a particular application. Figure 2, by way of example, presents a lumen 44 defining an angular blood flow path. However, a straight or curved blood flow path could also be used. See, for example, Figure 4. Advantageously, any difference between the inside diameter of the proximal end of the member 48 and the diameter of the lumen 44 at the proximal end 50 of the fluid return lumen 52 is minimized or eliminated to promote smooth circulation of blood.

Catheter portion 40 includes the distal portion of oxygen supersaturated fluid delivery tubing 54. Tubing 54 comprises at least one elongated, generally tubular member that includes a central lumen that defines a fluid flow path between a fluid intake port (not shown in Figure 2) made at the proximal end of the tubing. 54 and the fluid outlet port 56 made in the distal end 58 of the tubing 54. Catheter portion 40 could also include one or more stress and / or strain relief assemblies 60, 62.

The proximal end could be adapted to releasably engage a supply of oxygen supersaturated fluid. The fluid outlet port 56 could be made within the flow path defined by the fluid return lumen 52. Thus, a continuous fluid flow path is defined between the oxygen supersaturated fluid feed and a predetermined point within the body of a patient proximate the distal end of the fluid return lumen 52.

The portions near the fluid outlet port 56 of the fluid return lumen 52 and the distal end 58 of the tubing 54 are generally straight, and their longitudinal axes generally coincide, such that any difference in the direction of circulation of the blood in lumen 52 next to port 56 and the direction of flow of the outlet fluid through port 56.

As shown in Figure 2, the fluid outlet port 56 could be located sufficiently downstream of the proximal end 50 of the fluid return lumen 52 such that the fluid outlet port 56 avoids any disruption. of fluid circulation or non-laminar flow associated with the boundary between housing 42 and member 48 that could cause the formation of clinically significant gas bubbles. However, where any such non-laminar flow or circulation interruptions are minimized or eliminated, the outlet port for the oxygen supersaturated fluid could be disposed upstream of the proximal end of the fluid return lumen. See, for example, Figures 3 and 4. Furthermore, as shown in Figure 3, in an alternate embodiment, an oxygen supersaturated fluid line 54 could include a distal portion 66 that includes a fluid outlet port 68 at the outer boundary of lumen 44. For example, as shown in Figure 3, the longitudinal axis of the pipe 64 near the hole 68 and the longitudinal axis of the lumen portion 44 located downstream of the hole 68 advantageously coincide, while the longitudinal axis of the pipe 64 close to the hole 68 and the longitudinal axis of the lumen portion 44 located upstream of the hole 68 advantageously form an angle 70 comprising an acute angle that allows the smooth introduction of fluid from the pipe 64 to blood flow through lumen 44. Advantageously, angle 70 could be approximately thirty degrees, for example.

As shown in Figure 2, the portion of tubing 54 extending from the housing 42 to the blood flow path could be rigid enough to comprise a cantilevered member. However, as shown in Figure 4, the extending portion of the oxygen supersaturated fluid flow tubing 76 could also comprise a more flexible member that tends to naturally align itself within the lumen. 74 of blood circulation according to the path of least resistance. The distal end of tubing 76 could be supported in position or otherwise oriented within lumen 74 by one or two wings 72 extending between the distal end of supersaturated oxygen tubing 76 and the outer wall of lumen 74 which defines the limit. The flexibility and positioning of pipes 54 and 76 depend on the circumstances involved in a particular application, for example, hardness of the material, profile of the pipe, number of capillaries that make up the pipe, and the desired location of the outlet of the pipe. fluid.

The oxygen-supersaturated fluid is injected in such a way that jointly minimizes or avoids injury to blood cells. An example of an oxygen supersaturated fluid discharge is shown in Figure 5. Oxygen supersaturated fluid tubing 80 is disposed within fluid delivery lumen 84. The distal tip of tubing 80 is oriented within lumen 84 by one or more ribs or spacers 82 that support the distal portion of tubing 80. Tubing 80 includes one or more capillary tubes 86 (see Figure 5B) each of which includes a central lumen 88 through which oxygen-supersaturated fluid circulates. The configuration of the distal tip of tubing 80 advantageously minimizes or eliminates circulation interruptions that result from fluid outflow from each lumen 88 into the blood flow within lumen 84. By way of example, Figure 5B shows a tubing 80 comprising four capillary tubes 86 and including a distal tip of generally conical shape. The ends of each capillary tube 86 form an included angle 90 of about 52 degrees, for example. Capillary tubes could be constructed of polyamide-wrapped glass, with ground and polished distal ends

ES 2 296 396 T3 to help minimize or eliminate bubble formation and clinically significant fluid flow interruptions. Tubing 80 could include four 100 micron outside diameter by 350 micron inside diameter tubes, for example, epoxy embedded at their proximal and distal ends. However, the outer diameter could be in the range of about 20 to about 1,000 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 tubing 80 could vary depending on the circumstances involved in a particular application. Examples of possible configurations include, without limitation, flat, blunt, square, pencil-shaped, curved, parabolic, hyperbolic, and pyramidal configurations.

In the embodiment shown in Figure 6, the catheter includes an oxygen supersaturated fluid return line 100 and a blood collection assembly comprising a sheath 102 and a tube 108. The housing 104 includes a lumen 106 that forms a path. of blood circulation between the lights of the envelope 102 and tube 108. Tube 108 comprises the tubing that supplies blood to the blood pump (not shown in Figure 6) of the system. Tubing 100 is generally disposed centrally through housing 104 and within the central lumen of shell 102. Upon insertion of the distal portion of tubing 100 into a patient's body, sheath 102 is positioned within a vascular access sheath, guiding catheter, or other access device, such that the patient's blood can enter annular space 110 between the outer wall of tubing 100 and the interior wall of casing 102. The proximal end of tubing 100 could include a strain and / or strain relief assembly 112.

Figure 7 is a schematic diagram illustrating one use of the catheter system with a separate arterial access sheath 114. The wrap 114 could be one of many clinically approved arterial access wraps suitable for use in cardiovascular surgical procedures. Proximal end 116 of sheath 114 is adapted with an obturator or other such device that allows insertion of catheters, guide wires, or other surgical devices through sheath 114 and into the body without leakage. unnecessary blood supply. Blood drawn through lumen 118 of envelope 114 circulates via line 120 to blood pump 122 before being enriched and returned to the body. Blood returns through line 122 and catheter portion 126, where the flow of blood combines with an oxygen-supersaturated fluid flow through line 128 from a feed 130 to form a delivered oxygen-enriched fluid. to the patient through the distal portion 132 of the catheter system.

Figures 8 and 8A present an alternative embodiment of the catheter system. In accordance with this embodiment, a guiding catheter 140 including a distal tip (not shown), removably insertable within the body of a patient, is placed through an outer arterial access sheath 142. . The wrap 142 could be any one of the many types of clinically approved wraps that are typically used in cardiovascular surgical procedures to access the patient's vasculature. Guiding catheter 140 includes an inner liner 144. Inner liner 144 is deformable and could be removed either partially (not shown) or completely (see Figure 8A). When positive pressure is applied to lumen 146 of guiding catheter 140, for example, when angiographic dyes are introduced into lumen 146, and when liner 144 is in position covering blood intake ports 148 through the wall of the guiding catheter 140, the inner liner 144 presses against the intake ports 148 and closes them. When negative pressure is applied to lumen 146 of guiding catheter 140, for example, during blood collection from the patient, the inner liner deforms sufficiently to allow blood to enter lumen 146 through holes 148 of admission.

To facilitate the collection of blood from the patient, the fluid return line 150 could include a proximal portion 152 having smaller internal and external diameters than the distal portion 154 of the line 150. When the distal end of tubing 150 (not shown) is in position within a patient's body at a point near a predetermined zone, transition region 156 is disposed downstream of blood intake ports 148 in order to allow blood to enter lumen 146. Transition region 156 comprises a section of tubing 150 in which the external and internal diameters of tubing 150 increase along its length. To minimize or eliminate clinically significant bubble formation, downstream of transition region 156 the blood flow from tubing 150 combines with the oxygen supersaturated fluid exiting at end 188 of supersaturated fluid feed tubing 160 at oxygen. As described herein (see, for example, Figure 5), tube 160 could comprise either a single capillary tube, or a bundle of capillary tubes.

Figure 9 depicts part of a catheter system that includes an integral blood collection device comprising a porous and annular lateral blood intake 170. Catheter 172 could be used in conjunction with an access sheath or guiding catheter (not shown in Figure 9). Blood is drawn from the patient and passes through intake 170 into outer catheter lumen 174. From here, the blood circulates through a blood pump and is discharged back to the patient through the inner catheter lumen 176. As shown in Figure 9, the inner lumen 176 includes a proximal portion 178 having relatively smaller inner and outer diameters than the distal portion, and a transition region 182 joining the two portions. The oxygen supersaturated fluid feed tube 184 includes a fluid outlet port 186 disposed within the distal portion of the catheter 172. The fluid outlet tube 184 enters the blood flow within the lumen 176 downstream of any sudden pressure drops or other flow disturbances associated with the increase in the inside diameter of the lumen 176 in the transition region 182. Ribs or wings 188 or other centering device could be used to position the distal portion of tube 184.

IS 2 296 396 T3

In an alternative embodiment, as shown in Figure 10, the integral blood intake of a catheter 190 comprises an axial blood intake 192. Patient blood is drawn from within a sheath or guiding catheter, or directly from the patient's vasculature, through inlet 192, and into outer catheter lumen 194. From here, blood travels through a blood pump (not shown) and is returned to the patient through interior lumen 196. As shown in Figure 10, interior 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. The oxygen supersaturated fluid supply tube 204 includes a fluid outlet port 206 made within the distal portion 200 of the catheter 190, and ribs or wings 208 could be used to secure the distal portion of the tube 204 in place. Proximal portion 198 of inner lumen 196 could be secured within the interior of outer lumen 194 by an additional set of ribs or wings or other similar positioning device. As shown in Figure 10, proximal portion 198 of lumen 196 is free to naturally follow a path of least resistance through lumen 194. Proximal portion of tube 204 could similarly be clamped within lumen 196 or be free as shown.

Figures 11 and 11A through 11D present part of an example alternative catheter system that includes an integral blood collection device. A porous side intake 210 comprising a plurality of channels 212 traversing the outer wall of catheter 214 allows blood from the patient to enter the outer lumen 216. The blood contained in lumen 216 passes through a blood pump (not shown in Figure 11) before returning to the patient through lumen 218. Within lumen 218, the blood is combined with a fluid supersaturated in oxygen delivered through tube 220. As shown in Figure 11, tube 220, along at least a portion of its length, could be installed within lumen 218. The distal tip of the tube 220 is positioned along the longitudinal axis of the lumen 218 and is fixed in position by one or more fins or centering spacers.

Catheter 214 could include a lumen 224 through which blood could be drawn proximal to distal tip 226 of catheter 214, for example, to provide a blood sample for use in determining the pO2 of blood, or in monitoring of other clinical parameters, to ensure blood pressure at the distal end of the catheter, etc.

The distal tip 226 of catheter 214 includes an ultrasonic bubble detector 228 to detect the presence of clinically significant bubbles in oxygen-enriched fluid delivered to the patient's body by lumen 218. Accordingly, catheter 214 could also include one or more lights 230 within which conductors coupled to bubble detector 228 were installed.

Figures 12-14 illustrate examples of alternative catheter tip configurations. Figure 12 presents a straight tip portion 232 that includes a bubble detector 236 disposed near the tip 234 of the catheter. The bubble detector conductors 238 comprise one or more pairs of insulated wires or coaxial cables that could be arranged as shown, for example, in Figure 12A within the catheter side wall. Figure 13 illustrates a straight tip portion 240 including a dual bubble detector transducer 242, bubble detector leads 244, and a monorail guide light 246 through which a guidewire could be threaded (not shown ) to aid in the placement of the catheter within a patient's body. One transducer of a dual transducer-bubble detector assembly typically emits an acoustic pulse that is received by the other transducer, and the presence or absence of bubbles is determined by measuring the attenuation of the received signal. Figures 14 and 14A illustrate alternative configurations of a catheter tip that includes a monorail guide lumen 248. The catheter tip as shown in the drawings could include a relatively uniform wall thickness and be of a generally circular cross section (Figure 14) or it could have a variable wall thickness and assume a more teardrop-like shape (Figure 14 TO).

As shown in Figure 12, a catheter tip could also include a radiopaque band 250 to assist the physician or caregiver in positioning the device. Typically, band 250 comprises one or more metals or metal alloys, eg, platinum, gold, tungsten, and iridium, and platinum-iridium and other high density materials that are visible under fluoroscopy.

A further example bubble detector transducer 252 is presented in Figures 15 and 15A. The transducer 252, which could be attached or otherwise fixedly attached to or within the distal portion of the catheter, could include a single transducer that can function In a pulse echo mode, that is, it can send an acoustic pulse and detect its reflection. Transducer 252 includes an inner sleeve 254, a wrapped piezoelectric film layer 256, a metal band 258, and an outer sleeve 260. The inner sleeve 254 comprises a polyamide sleeve. The wrapped film 256 comprises a metallized polyvinylidene polyfluoride film, which includes a conductive upper layer 262, a conductive lower layer 264, and an insulating inner layer that separates the upper and lower layers. As shown in the drawings, the metallized film is bent and then wrapped at least once (typically about two to five times) around the inner sleeve 254. This bend allows the use of thinner film that exhibits higher capacitance and lower impedance than a more conventional transducer such that cable conductors 266, which are long, thin cables, can be installed better. The cable conductors 266 are connected to the outermost surfaces of the layers 262, 264 with a conductive epoxy resin 268. The band 258 could comprise an aluminum foil or a metal band that reflects the acoustic impulse emitted outwards. The band 258 comprises a radiopaque material so that the band can act as a marker to promote device placement. The outer jacket 260 could be constructed of Pebax or other suitable material that provides support to the structure. In addition, it should be understood that the

ES 2 296 396 T3 bubbles illustrated in Figures 15 and 15A is advantageously a compact device, that is, the air gaps between the layers of the bubble detector have been minimized or eliminated. For example, the air voids could be filled with an epoxy resin or other suitable filling material.

Electronic circuitry 271 associated with bubble detector transducer 252 causes transducer 252 to emit ultrasonic pulses typically in the 20-30 MHz range. In pulse echo mode, these ultrasonic pulses are transmitted in a pulse train that they have a frequency of approximately 20-50 kHz. In this way, approximately ten reflections could be sampled from a single bubble as it passes through the transducer 252, which is about 1 to 1.5 millimeters in length. After the pulses of ultrasonic energy have discharged for a positive portion of this duty cycle, the circuits 271 wait approximately 0.5 microseconds to allow a "hand signal" period. The reflected signals could then be measured, typically for at least three reflected pulses, before emitting the next ultrasonic signals.

The present invention has been described in connection with exemplary embodiments. In accordance with the present invention, the operational parameters for the system could be varied, typically with a physician or caregiver specifying and selecting them for the desired clinical indication. Furthermore, it is contemplated that other embodiments, which those skilled in the art could readily devise based on the knowledge specified herein, could fall within the scope of the invention which has been defined by the appended claims. The present invention could be modified and practiced in different but equivalent ways, which will be apparent to those skilled in the art who reap the benefits of the knowledge specified herein.