ES2375973T3 - APPARATUS AND METHOD FOR BLOOD OXYGENATION. - Google Patents

Abstract

A device for oxygenating blood and administering oxygenated blood to a patient, including the device: a blood pump assembly (20) coupled to a blood supply (10); a blood oxygenation assembly (30) coupled to the blood pump assembly (20), the blood oxygenation assembly (30) receiving the blood from the blood pump assembly (20) and oxygenating the blood; an administration system (40) coupled to the blood oxygenation assembly (30), the administration system (40) being adapted to administer the oxygenated blood to a patient, including the administration system (40): a generally elongated element tubular (700) having a proximal end portion (710) and a distal end portion (720), the distal end portion (720) being adapted to be inserted into the patient and the proximal end portion (710) being coupled to the blood oxygenation assembly (30), the element (700) also having a first lumen (760) for transporting the oxygenated blood that generally extends from the proximal end portion (710) to the distal end portion (720 ), and the element (700) having a transition portion (750) located between the proximal end portion (710) and the distal end portion (720), characterized in that the transition portion (750) is relatively flexible compared to the proximal end portion (710) and is relatively rigid compared to the distal end portion (720).

Description

Apparatus and method for blood oxygenation

Field of the Invention

The present invention relates generally to a system for oxygenating blood, and more particularly, to a system for providing oxygenated blood, for example, hyperoxemic or hyperbaric blood, to a patient.

Background of the invention

Oxygen is a crucial nutrient for human cells. Cell damage can be due to lack of oxygen for even short periods of time, which can lead to organ dysfunction or failure. For example, victims of heart attack and stroke experience obstructions or deviations in blood flow that prevent oxygen from being distributed to vital tissue cells. Without oxygen, the heart and brain deteriorate progressively. In severe cases, death occurs due to complete organ failure. Less severe cases typically involve expensive hospitalization, specialized treatments and prolonged rehabilitation.

Blood oxygen levels can be described in terms of the concentration of oxygen that would be achieved in a saturated solution at a given partial pressure of oxygen (pO2). Typically, for arterial blood, normal blood oxygen levels (i.e. normoxia or normoxemia) are in the range of 90-110 mm Hg. Hypoxemic blood (i.e. hypoxemia) is arterial blood with a pO2 of less than 90 mm Hg. Hyperxic 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 , 85 (2): 828-38, 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 134 (3): 544- 50) Hyperbaric blood is arterial blood with a pO2 greater than 760 mm Hg. Venous blood typically has a pO2 less than 90 mm Hg. In the average adult, for example, normal levels of oxygen in venous blood are in the range general from 40 mm Hg to 70 mm Hg.

Blood oxygen levels could also be described in terms of hemoglobin saturation levels. For normal arterial blood, hemoglobin saturation is approximately 97% and varies only slightly as pO2 levels increase. For normal venous blood, 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 may occur. When the infarction manifests itself in a heart attack, the coronary arteries fail to provide adequate blood flow to the heart muscle.

The treatment of acute myocardial infarction or myocardial ischemia often includes performing angioplasty or stent implantation in the vessels to compress, cut or otherwise treat the occlusion (s) within the vessel walls. For example, a successful angioplasty uses a balloon to increase the size of the vessel opening to allow increased blood flow.

Even with the successful treatment of occluded vessels, there may still be a risk of tissue injury. During percutaneous transluminal 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. Reperfusion injury can also occur, for example, due to slow coronary reflux or absence of reflux after angioplasty.

For some patients, angioplasty procedures are not an attractive option for the treatment of blocked vessels. Such patients are typically at an increased risk of ischemia for reasons such as poor left ventricular function, type and position of the lesion, or the amount of myocardium at risk. Treatment options for such patients thus include more invasive procedures such as coronary bypass surgery.

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

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, the tolerated balloon inflation time can be increased by the concurrent introduction of oxygenated blood to the patient's coronary artery. Increased blood oxygen levels can also subject left ventricular cardiac tissue normally perfused to hypercontractility to further increase blood flow through the vessels.

treated coronaries.

Infusion of oxygenated blood or oxygen-enriched fluids can also be continued after the termination of PTCA treatment or other procedures (for example surgery) where there has been "stunning" of cardiac tissue with associated risk of function. In some cases, continuous infusion can accelerate the reversal of ischemia and facilitate the recovery of myocardial function.

Conventional methods for the administration of oxygenated blood or oxygen-enriched fluids to tissues at risk involve the use of blood oxygenators. Such procedures generally involve drawing blood from a patient, circulating it through an oxygenator to increase the concentration of oxygen in the blood, and subsequently 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 the use of a conventional oxygenator in an extracorporeal circuit to oxygenate blood. Such systems are typically expensive, complex and difficult to operate. Often a qualified perfusionist has to prepare and supervise the system.

Conventional oxygenators also typically have a large volume of priming, that is, the total volume of blood contained within the oxygenator, the tubes and other system components, and associated devices. It is not unusual in the case of a typical adult patient that the oxygenation system maintains more than one to two liters of blood. Such large volumes of priming are undesirable for many reasons. For example, in some cases a blood transfusion may be necessary to compensate for the blood temporarily lost in the oxygenation system because of its large volume of priming. Often heaters should be used to keep the blood temperature at an acceptable level as it progresses through the extracorporeal circuit. In addition, conventional oxygenators are relatively difficult to turn on and off. For example, if the oxygenator is turned off, large stagnant pools of blood could be coagulated in the oxygenator.

In addition, with extracorporeal circuits including conventional blood oxygenators there is a relatively high risk of reaction of cell inflammation and blood clotting due to the relatively slow rates of blood flow and the large surface area of blood contact. A surface area of blood contact of approximately 1-2 m2 and velocities of approximately 3 cm / s are not unusual in conventional oxygenator systems. Thus, relatively aggressive anticoagulation therapy, such as heparinization, is generally required as an adjunct to using the oxygenator.

Perhaps one of the major disadvantages of 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. Thus, with conventional oxygenators, blood levels of pO2 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 134 (3): 544-50. These studies have generally involved placing patients in pressurized pure oxygen chambers at up to 2 atmospheres, resulting in systemic oxygenation of the patient's blood above a pO2 level of approximately 1200 mm Hg. However, the use of hyperbaric oxygen therapy after restoration of coronary artery permeability in the position of an acute myocardial infarction is impractical. Supervising critically ill patients in a hyperbaric oxygen chamber is difficult. Many patients are claustrophobic. Ear damage may occur. In addition, treatment times longer than 90 minutes cannot be obtained without concern for pulmonary oxygen toxicity.

For these reasons, the treatment of ischemia of regional organs has not been developed clinically in general. Thus, there remains a need for a simple and convenient system to administer oxygenated blood and other fluids to patients for the localized prevention of ischemia and the treatment of post-ischemic tissue and organs.

WO 99/08733 describes a system and method for generalized extracorporeal support including a tube through which the patient's blood circulates and is mixed with supersaturated fluid with oxygen.

Thus, according to one aspect, a problem is to provide a device that can oxygenate blood and deliver the oxygenated blood to a patient in a suitable condition, that is, with an appropriate temperature, pressure, quantity and without significant clinical bubbles.

This problem is solved with a device having the characteristics described in claim 1. Preferred embodiments are defined in the dependent claims.

Summary of the Invention

The present invention can solve one or more of the problems set forth above. Some possible aspects of the present invention are set forth below as examples. It should be understood that these aspects are presented simply in order to provide the reader with a brief summary of some forms that the invention could take and that these aspects are not offered in order to limit the scope of the invention. In fact, the invention may encompass a variety of aspects that may not be set forth below.

In one embodiment of the present invention, a system for the preparation and administration of oxygenated blood is provided. In applications that involve the prevention of ischemia or the treatment of ischemic tissues, the system can be used for the preparation and administration of oxygenated blood at a specific position within the patient's body. The system may include an extracorporeal circuit to oxygenate blood, for example, increase the level of oxygen in the blood, in which the blood to oxygenate is blood drawn from the patient. The system can also be used advantageously for regional or localized administration of oxygenated blood.

Factors that influence the determination of blood flow characteristics for the extracorporeal circuit may include one or many other clinical parameters or variables of the oxygenated blood to be delivered to the patient, for example, the size of the patient, the percentage of general circulation to be provided, the size of the blank to be accessed, hemolysis, hemodilution, pO2, pulsatility, mass flow rate, volumetric flow rate, temperature, hemoglobin concentration and pH.

Intervention devices (catheters, infusion guide wires, etc.)

The system may include an administration set including an elongated, generally tubular assembly, including a central lumen and at least one end that can be placed inside the patient's body near the site of tissue to be treated, including the end of an outlet port for oxygenated blood . The administration set advantageously includes a catheter that defines a fluid path, including a proximal portion adapted to engage an oxygenated blood supply assembly, and a distal portion that defines a removably insertable fluid path within the patient's body, for infuse oxygenated blood to predetermined places. Alternatively, the administration set may include an infusion guide wire, sheath, or other similar intervention device of the type used to administer fluids to patients.

The embodiments may be used in conjunction with angiographic or guide catheters, arterial envelopes, and / or other devices used in angioplasty and other cardiovascular intervention procedures. The system can be used in applications that involve one or more vascular holes, that is, in contralateral or ipsilateral procedures.

In contralateral procedures blood is drawn from the patient in a first position, for example, the left femoral artery. The oxygenated blood is returned to the patient in a second position close to the tissue to be treated. The oxygenation of the blood takes place when the blood pumped through the extracorporeal circuit or loop passes through a set of oxygenation and forms the oxygenated blood to be administered. In applications where the system includes a catheter, the catheter may include a removable distal end insertable into the patient's body through a second position, such as the patient's right femoral artery. The distal end includes at least one hole in fluid communication with the central lumen and through which the oxygenated blood can flow out. In addition, the distal catheter portion may be provided with a shaped tip portion in order to facilitate the introduction of the device, such as through the same envelope used for intervention procedures analogous to angioplasty, at specific predetermined positions within the patient body Examples of tip tip shapes that can be used include any of the clinically accepted standard tip configurations used with guiding catheter-like devices to provide access and maintenance in positions such as the coronary ostium. Accordingly, the method may further include the step of placing the distal end portion of the catheter including the fluid outlet orifice in a predetermined position within the patient's body next to the tissue to be treated.

In ipsilateral procedures, the system can be used in conjunction with one or more suitable guide catheters and / or introducer shells, of standard size, clinically accepted. The system, for example, may include a catheter, a guide catheter and catheter, or a catheter and shell, for use within an introductory guide or catheter catheter used for the primary intervention procedure.

The administration set advantageously includes a catheter suitable for sub-selective administration of oxygenated blood. However, the realization of a catheter selected for use will depend on the circumstances involved in a particular application. For example, in some cases involving the prevention of myocardial ischemia or the treatment of ischemic myocardial tissues, a selective or non-selective catheter may be preferable.

Administration of oxygenated blood can take place by means of a "simple" intervention device (for example, an infusion guide catheter or wire) or an administration device or lumen associated with or that is part of a multi-component set operable for performance of diagnostic and / or therapeutic procedures (ie, in addition to the administration of oxygenated blood). Examples of such sets include, without

limitation, stent placement devices, angioplasty balloon catheters, radiation delivery systems, medication delivery devices, etc. Flow rates of about 25 ml / minute to about 200 ml / minute for oxygenated blood may be advantageous, in particular from about 75 ml / minute to about 125 ml / minute.

Fluid Administration Routes

Advantageously, oxygenated blood is supplied to a particular position desired by a fluid delivery apparatus including: (1) a generally elongated fluid delivery assembly having a proximal section and a distal section, the distal section including a portion at least partially removably insertable within the patient's body, including the removably insertable portion of at least one fluid outlet orifice in fluid communication with a fluid delivery lumen extending between the proximal section and the removably insertable portion of the fluid delivery assembly ; and (2) a fluid conduit having: a first end portion for receiving a blood supply at the outlet of a blood pump operatively coupled to the fluid conduit; a second end detachably coupled to the fluid delivery lumen of the fluid delivery assembly; and an intermediate portion between the first and second ends adapted to oxygenate the blood supply; The fluid conduit and the fluid delivery lumen define a continuous fluid path between the first end portion of the fluid conduit and the fluid outlet orifice (s). Advantageously, the fluid delivery apparatus provides oxygenated blood, and very advantageously hyperoxemic or hyperbaric blood, to a patient without potentially clinically significant gas bubbles in the blood. More advantageously, the fluid delivery apparatus can provide a patient with oxygenated blood that has a pO2 greater than about 760 mm Hg but less than pO2max for a given rate of blood flow Qsangre, where pO2max is equal to the maximum back pressure generated within of the fluid delivery apparatus by operation of the blood pump to achieve the blood flow rate.

In one embodiment, the intermediate portion of the fluid conduit adapted to oxygenate the blood supplied by the blood pump, that is, the oxygenation assembly, may include a high pressure membrane oxygenator. In another embodiment, the intermediate portion of the fluid conduit includes an assembly including a mixing region in which an oxygenated fluid, for example, a supersaturated fluid with oxygen, is combined with the blood to effect direct liquid to liquid oxygenation. In another embodiment, the intermediate portion may include an assembly to combine two fluid streams (for example, an apparatus that generally resembles a Y-tube, T-adapter, or the like), the assembly adapted to couple to systems of administration to supply blood to oxygenate and to supply oxygenated blood or other fluids.

Accordingly, the fluid delivery apparatus may advantageously include a first portion of tube that extends between a blood pump and an oxygenation assembly; the oxygenation assembly; a second tube portion extending between the oxygenation assembly and the proximal end of a fluid delivery assembly; and the fluid administration set.

In a patient who breathes air through the lungs, the dissolved gases in the patient's blood (nitrogen, N2; carbon dioxide, CO2; and oxygen, O2) are equal to atmospheric pressure. Chemically, this relationship is indicated by the equation

Ptotal, = pN2 + pCO2 + pO2

where Ptotal is the atmospheric pressure and the right side of the equation represents the relative, or partial, pressures of gases dissolved in air. The above equation is approximately balanced as follows:

760 mmHg = 600 mmHg + 45 mm Hg + 115 mmHg

For blood including dissolved gases that have the partial pressures set forth above, during a hyperoxygenation process that takes place in the intermediate portion of the fluid conduit, the pO2 is high and the Ptotal may exceed the atmospheric pressure. For example, if the pO2 increases to 800 mm Hg without changing pN2 and pCO2, the Ptotal would be equal to 1445 mm Hg, an increase of almost double.

The fluid pressure at the outlet of the intermediate portion of the fluid conduit, Pfluid, is a measure of the differential pressure through the portion of the fluid conduit between that position and the fluid outlet orifice (s) plus outlet pressure. To avoid the formation of potentially clinically significant gas bubbles, it is especially advantageous to raise the fluid pressure at the outlet of the intermediate portion of the fluid conduit to a level that exceeds the total dissolved gas pressure. Thus, administration of oxygenated blood can take place without bubbles, that is, without the formation of potentially clinically significant bubbles, where Pfluid> Ptotal.

Since most of the pressure measurements use gauge pressures (i.e. gauge pressure = total pressure minus atmospheric pressure), the ratio for administration without bubbles can also be simplified and approximate ΔPluid> PO2 (out), where pO2 ( out) is the pO2 of the oxygenated blood to be administered to the patient. In others

terms, a caregiver only has to compare two simple measurements, ΔPfluid and pO2 (out), to ensure administration without bubbles during a procedure.

Experimental data support the use of the simplified and approximate ΔPfluid> PO2 (out) relationship to achieve bubble-free administration. As set forth in Table I, a fluid delivery apparatus was used including a set of liquid to liquid oxygenation with two catheters having different effective diameters to infuse oxygenated blood to the left coronary vasculature of a 40 kg pig to determine if the The relationship between ΔPfluid and pO2 (out) affects the formation of bubbles during the infusion of oxygenated blood. In tests where ΔPfluid> pO2 (out), no bubbles were observed using 2D echocardiography during the infusion of oxygenated blood, and an ultrasonic bubble detection system did not detect bubbles larger than about 100 μm in diameter. On the other hand, in tests where ΔPfluid <pO2 (out), 3-4 bubbles per heartbeat were observed in the right atrium using 2D echocardiography during the infusion of oxygenated blood, and the ultrasonic bubble detection system detected numerous bubbles of more than about 100 μm in diameter.

Table I

Blood flow (ml / minute)

Blood / oxygenated fluid (flow rate ratio of dimensionless fluid) ΔPluid pO2 (out) Ultrasonic bubble event (#) 2D echo bubbles (# / heartbeat)

78

52 843 783 0 0

78

52 819 723 0 0

103

47 1043 834 0 0

104

35 1031 982 0 0

107

36 311 987 32 3-4

107

36 315 1031 fifteen 3-4

152

51 449 771 24 3-4

152

51 460 741 69 3-4

Typically, pO2 (out) can be selected by the caregiver based on the circumstances involved in a particular application. Thus, bubble-free administration can be ensured by selecting an appropriate fluid delivery apparatus, that is, one that can effect a fluid pressure drop that exceeds the desired pO2 selected for a rate down from the intermediate portion of the fluid conduit. given blood flow. In addition, the drop in fluid pressure may vary depending on factors such as the duration of fluid administration and the geometry of the fluid lumen (for example, internal diameter, taper, cross-sectional profile, etc.), factors that may vary depending on the specific application involved. Thus, it may be useful (for example, to promote ease of selection) to characterize all or a portion of the fluid delivery apparatus down the intermediate portion of the fluid conduit in terms of an effective diameter, or in terms of levels of pO2 achievable for a given oxygenation set and / or conditions given at the outlet of the intermediate portion of the fluid conduit.

For example, according to an embodiment of the present invention, for an exemplary device for administration of oxygenated blood fluid, the pressure of the oxygenated blood in the oxygenation assembly is a function of the blood flow rate and the effective diameter of the catheter. For an oxygenated blood fluid delivery apparatus, the relationship between blood flow rate and oxygenated blood pressure in the oxygenation set for a given catheter can be determined using the Hagen-Poiseuille law:

πΔPD4 Q =

128Lη

which generally controls laminar fluid flows through ducts, in which Q = volumetric flow rate; L = duct length; D = inner diameter of the duct; η = viscosity of the fluid; and ΔP = pressure difference across the length of the duct. Other embodiments may also be used depending on the circumstances involved in a particular application, for example, an embodiment for turbulent flow applications, for which the relationship between blood flow rate and oxygenated blood pressure in the oxygenation assembly is You can determine using models that control turbulent flow.

In general, with a given oxygenated blood fluid delivery apparatus, for a constant rate of blood flow Qsangre, when the effective inner diameter of the catheter increases, the pressure of the Pfluid blood (gauge) in the oxygenation assembly decreases. Knowing the simplified and approximate ratio of administration without bubbles, ΔPfluid> pO2 (out), a caregiver having a catheter characterized by effective inner diameter can determine whether an appropriate range of blood flow rates can be achieved if the caregiver used a device of fluid delivery including the catheter to deliver blood that has a desired pO2. Alternatively, a caregiver who specifies a desired oxygenated blood pO2 and a range of oxygenated blood flow rates may select a catheter for use in a fluid delivery apparatus for a particular application.

High pressure membrane oxygenation assemblies

In one embodiment, the system advantageously includes a membrane oxygenator assembly and assemblies for supplying controlled flows or supplies of oxygen and blood gas. Advantageously, the intermediate portion of the fluid conduit includes a membrane oxygenator assembly operable at high pressures, that is, oxygen and blood gas supply pressures within the membrane oxygenator assembly exceeding atmospheric pressure.

The assembly for supplying controlled flows or supplies of oxygen gas advantageously includes a regulated source of oxygen gas, so that oxygen gas is distributed to the membrane oxygenator assembly at a pressure greater than atmospheric pressure. Advantageously, oxygen gas is supplied to the membrane oxygenator assembly at a pressure greater than atmospheric pressure and less than about 50 psia, the approximate maximum pressure that can be generated by commercially available blood pumps that administer blood. The assembly for supplying controlled oxygen gas flows or supplies may be one of the many commercially available and clinically accepted oxygen delivery systems suitable for use with human patients (eg, regulated bottled oxygen).

The assembly for supplying controlled blood flows or supplies advantageously includes a blood source in combination with means for providing blood to the membrane oxygenator assembly. Advantageously, the blood to be oxygenated includes blood drawn from the patient, so that the blood delivery assembly includes a blood inlet arranged along a portion of a catheter or other similar device insertable at least partially removable into the body. of the patient; a pump loop that in combination with the catheter or other device defines a continuous fluid path between the blood inlet and the membrane oxygenator assembly; and a blood pump to control blood flow through the pump loop, that is, the blood flow provided to the membrane oxygenator assembly. The blood pump can be one of the many commercially available and clinically accepted blood pumps suitable for use with human patients. An example of such a pump is the 6501 RFL3.5 Pemco peristaltic pump that can be obtained from Pemco Medical, Cleveland, Ohio.

The system provided advantageously includes an oxygenated blood supply assembly including a membrane oxygenator assembly including at least one membrane that separates within the membrane oxygenator assembly the oxygen gas provided by the oxygen gas supply assembly and the blood provided by the assembly of blood supply, and through which oxygen and other gases can diffuse. Advantageously, the oxygen gas is administered to the "gas side" of the membrane oxygenator assembly by the oxygen gas supply assembly at a gas side pressure greater than atmospheric pressure; the blood delivery assembly provides a blood supply to the "blood side" of the membrane oxygenator assembly at a blood side pressure greater than the gas side pressure; and the oxygen gas and at least a portion of the blood supply is kept in contact with the membrane so that oxygen diffuses through the membrane and dissolves in the blood supply.

The membrane may include a solid material (for example, silicone rubber) or a microporous material (for example, a polymeric material, such as polypropylene). Advantageously, the blood side pressure is maintained at a higher level than the gas side pressure to prevent the flow of bulky gas through the membrane. However, lower blood side pressures can be used if a solid, non-porous membrane is used. The type of membrane used, and the gas and blood side pressures (which can be defined, for example, by a given differential pressure across the membrane) may vary depending on the circumstances involved in a particular desired application.

The gas side of the membrane oxygenator assembly can operate in an "open" or "closed" mode. In open mode, a gas side stream including oxygen gas provided by the oxygen gas supply assembly "sweeps" the gas side of the membrane oxygenator assembly. During the sweep, oxygen is diffused through the membrane to dissolve in the blood, and blood gases such as carbon dioxide and nitrogen can diffuse through the membrane to join the gas side stream. The gas side stream exits the membrane oxygenator assembly through a hole or other outlet fluid conduit. In closed mode, the hole or other outlet fluid conduit is closed to prevent gas leakage from the gas side of the membrane oxygenator assembly.

In an alternative embodiment, the membrane oxygenator assembly includes a gas inlet but is not provided with a vent hole or other fluid outlet duct of the gas side stream. This alternative embodiment thus includes a closed mode device. In closed mode operation the gas side pressure is advantageously equal to the pressure at which the oxygen gas supply assembly provides oxygen gas to the membrane oxygenator assembly. In open mode the gas side pressure falls through the membrane oxygenator assembly, although perhaps only slightly, from the pressure at which the oxygen gas supply assembly provides oxygen gas to the membrane oxygenator assembly.

The membrane oxygenator assembly is advantageously sized depending on the circumstances involved in a particular desired application. For example, for an administration flow of oxygenated blood less than 0.3 liters per minute, an active membrane surface area much less than two square meters is required (the approximate active membrane surface area for a conventional adult sized oxygenator capable of handling six liters of blood per minute). By way of example, and without limitation of the scope of the present invention, the factors that affect the dimensions of the membrane oxygenator assembly include the desired oxygen level for the flow rate of blood to be oxygenated and of oxygenated blood.

The system provided advantageously supplies oxygenated blood from the membrane oxygenator assembly to a given location without the formation or release of clinically significant oxygen bubbles. The administration of oxygenated blood in a given place without formation or release of clinically significant bubbles can be advantageously performed by selecting the catheter material, using an administration catheter of appropriate dimensions, and / or conditioning it to remove places. of nucleation. The exact material, size and conditioning procedure may vary depending on the circumstances involved in a particular application. For administration of approximately 3 ml / second of oxygenated blood with a membrane oxygenator assembly operating at a gas side pressure of approximately 50 psi, a catheter of a length of approximately 130 cm and an internal diameter of approximately 40 thousandths of an inch it would provide a gradual reduction in pressure that can help prevent the release of potentially clinically significant gas bubbles.

The device according to the invention can be used in a method for the preparation and supply of oxygenated blood. Said method for enriching blood with oxygen includes providing a membrane having first and second sides; providing oxygen gas in contact with the first side of the membrane at a pressure P1 greater than atmospheric pressure; provide on the second side of the membrane a blood supply at a pressure P2 greater than P1; and keeping at least a portion of the blood supply in contact with the second side of the membrane so that oxygen is diffused through the membrane and dissolved in the blood supply. Advantageously, the pressure P1 is higher than the atmospheric pressure and less than about 50 psia. The method also advantageously includes providing a current including oxygen gas in contact with the first side of the membrane. Advantageously, the current maintains contact with the first side of the membrane so that a gas (for example, carbon dioxide, nitrogen, water vapor, etc.) in the blood supply diffuses through the membrane and joins the stream.

The device according to the invention can be used to deliver oxygenated blood to a specific place within the patient's body. The method includes raising the level of pO2 in blood to be delivered to the patient and administering said blood to a given place. The method may include the step of controlling or providing controlled amounts of blood and oxygen gas to a membrane oxygenator assembly in order to produce oxygenated blood for administration to a specific predetermined location. Blood oxygen levels (e.g., pO2) can be maintained, adjusted or otherwise controlled by controlling flow rates or by providing controlled amounts of blood and / or oxygen gas. Thus, a blood-gas control method is provided.

Liquid to liquid oxygenation set

In another embodiment, the intermediate portion of the fluid conduit adapted to oxygenate the blood supplied by the blood pump includes an assembly including a mixing region in which an oxygenated fluid, for example, a fluid supersaturated with oxygen, is combined with the blood. Advantageously, the mixing region is defined by a chamber-like assembly including an injection zone in which the oxygenated fluid is mixed with the blood at a pressure higher than the desired blood pO2. The oxygenation of the blood takes place as a result of convective mixing that involves the two fluids in contact and to a lesser extent as a result of oxygen that diffuses directly from the oxygenated liquid to the blood, that is, dispersion. The mixture is advantageously a convective mixture that takes place quickly and completely.

In one embodiment, the chamber-like assembly includes a mixing chamber including a generally elongated cylindrical or tubular assembly having upper and lower ends, each end having a plug or similar device fixedly attached, in order to define an interior space at. Advantageously, the mixing chamber includes in fluid communication with the interior space a first inlet port adapted to receive a supply of blood to be oxygenated; a second inlet port adapted to receive a supply of oxygenated fluid to be mixed with the blood; and an outlet port adapted for administration of the oxygenated blood to a particular desired position.

To promote the mixing of blood and oxygenated fluid within the interior space of the chamber, the blood to be oxygenated advantageously enters the mixing chamber from a position and in a direction so that a vortex or cyclonic flow of blood is created within the camera. Advantageously, blood enters the chamber along a substantially tangential path to the chamber wall. Advantageously, the oxygenated liquid enters the chamber near the blood inlet, and the oxygenated blood leaves the chamber through a hole in the lower part of the chamber. More advantageously, the oxygenated liquid enters the chamber in a generally upward direction normal to the initial direction of travel of the blood entering the chamber.

The mixing chamber is advantageously pressurizable, the lower portion of the chamber accumulating a blood supply and the upper portion including a gas charge. The gas charge advantageously helps cushion the pulsatility of the blood entering the chamber.

The oxygenated fluid advantageously includes a supersaturated oxygen fluid in which the dissolved oxygen content will occupy a volume between about 0.5 and about 3 times the volume of the standardized solvent at standard temperature and pressure. Examples of solvents that can be used include saline, lactated Ringer's solution, and other aqueous physiological solutions. The oxygenated fluid is advantageously distributed to the mixing chamber by one or more capillaries having an internal diameter in the range of about 15 to about 700 µm (advantageously, about 100 µm), the capillaries forming a continuous fluid flow path between the mixing chamber and a supply or assembly to provide a supply of the oxygenated fluid.

The oxygenated fluid will typically be supplied to the mixing chamber according to parameters specified and selected by the caregiver for the desired clinical indication. The flow of oxygenated fluid is generally constant and continuous, although variable or intermittent flows can be used. The flow rates can be in the range of about 0.1 cc / minute to about 40 cc / mm, although especially advantageous flow rates can be between about 2 cc / minute and 12 cc / minute. The normalized oxygen concentrations at standard temperature and pressure may be in the range of about 0.1 ml of O2 per ml of physiological solution to approximately 3 ml of O2 per ml of physiological solution, although especially advantageous concentrations may be approximately 1 ml. of O2 per ml of physiological solution.

The device according to the invention can be used for the preparation and administration of oxygenated blood. The method includes providing a chamber assembly in which blood and an oxygenated liquid, for example, a supersaturated liquid with oxygen, are mixed under pressure to form oxygenated blood. The method may include the step of controlling or providing controlled amounts of blood and oxygenated liquid to the chamber assembly to maintain, adjust or otherwise control blood oxygen levels. Thus, an alternative method of blood-gas control is provided.

Temperature

Oxygenated blood is advantageously supplied to the patient at approximately 37 ° C, that is, the operation of the system does not significantly affect the temperature of the patient's blood. However, in some cases, it may be desirable to cool the oxygenated blood, for example, to induce local or regional hypothermia (for example, temperatures below about 35 ° C). By way of example only, in neurological applications such cooling may be desirable to achieve a neuroprotective effect. Hypothermia can also be considered as an advantageous treatment or preservation technique for ischemic organs, organ donations, or reduce metabolic demand during periods of reduced perfusion.

Accordingly, the system provided may include an operable heat exchanger assembly to maintain, increase or decrease the temperature of the oxygenated blood as desired in view of the circumstances involved in a particular application. Advantageously, temperatures of oxygenated blood in the range of about 35 ° C to about 37 ° C will be generally desired, although blood temperatures outside that range (eg, perhaps only 29 ° C or more) may be more advantageous provided that the patient's central temperature remains at safe levels in view of the circumstances involved in the particular application. Temperature monitoring can take place, for example, with one or more thermocouples, thermistors or temperature sensors integrated in the electronic circuitry of a controlled feedback system, so that an operator can enter a desired perfusion temperature over time. expected response of the system for seconds or minutes depending on infusion flow rates and other parameters associated with the active infusion of cooled oxygenated blood.

Examples of heat exchange assemblies suitable for use with the present system, alone or integrated with a system component, include any of the numerous commercially available and clinically accepted heat exchange systems in current blood delivery systems, by for example, heat exchangers, heat irradiation devices, convective cooling devices and closed cooling devices. Such devices may include, for example, conductive / convective heat exchange tubes, typically made of stainless steel or high strength polymers, in contact with

blood on one side and with a refrigerant on the other side.

In another embodiment, in a set of liquid to liquid oxygenation, cooled oxygenated blood can be obtained by mixing blood with a cooled oxygenated liquid, for example, a supersaturated liquid with oxygen. Any commercially available and clinically acceptable heat exchange system can be used to cool the oxygenated liquid and / or cool the oxygenated blood. Since most gases have greater solubility when dissolved in aqueous liquids at low temperatures (for example, the solubility of oxygen in water increases at a rate of 1.3% per degree Celsius decrease), this method offers the benefit added better stability of oxygenated blood, which in some cases may allow higher concentrations of

10 oxygen

Bubble detection sets and others

The system may include one or more gas bubble detectors, of which at least one is capable of detecting the

The presence of microbubbles, for example, bubbles with diameters from about 100 µm to about 1000 µm. In addition, the system may include one or more macrobubble detectors to detect larger bubbles, such as bubbles with diameters of approximately 1000 µm or more. Such macrobubble detectors may include any suitable commercially available detector, such as a tube mounted, external bubble detector, including two transducers that measure the attenuation of a sound pulse.

20 that advances from one side of the tube to the other. Such a suitable detector can be purchased from Transonic Inc., of New York.

Microbubble and macrobubble detectors provide the doctor or caregiver with a warning of the possible generation of clinically significant bubbles. Such warnings can also be obtained through the use of 2D transthoracic echo (for example, to seek clarification of the echo of myocardial tissue) and the supervision of

25 other patient data.

Advantageously, the bubble detection system is able to discriminate between bubbles of various sizes. In addition, the bubble detection system operates advantageously continuously and is operatively coupled to the general system so that a general shutdown of the system takes place at the detection of a

30 macrobubble

The system may also include several conventional elements, such as sensors, flowmeters (which can also serve a dual function as a macrobubble detector), or other clinical parameter monitoring devices; hydraulic components such as accumulators and valves to manage flow dynamics; 35 access ports that allow fluid extraction; filters or other safety devices to help ensure sterility; or other devices that can generally help control the flow of one or more of the fluids in the system. Advantageously, these devices are placed within the system and used to prevent the formation of clinically significant bubbles within the fluid flow paths, and / or to avoid fluid flow disturbances, for example, capillary blockages or other fluid paths. In addition, the

The system advantageously includes a biocompatible system acceptable for clinical use with human patients.

Brief description of the drawings

Other objects and advantages of the present invention will be apparent from reading the following detailed description 45 and by reference to the accompanying drawings in which:

Figure 1 is a schematic diagram illustrating an exemplary embodiment of a system for oxygenating blood according to the present invention.

Figure 2 is a schematic diagram illustrating an exemplary embodiment of a blood oxygenation assembly including a high pressure membrane oxygenator according to the present invention.

Figure 3 is a cross-sectional view of an exemplary embodiment of a high pressure membrane oxygenator according to the present invention.

Figure 4 is a schematic diagram illustrating an exemplary embodiment of an extracorporeal circuit including a blood oxygenation system having a high pressure membrane oxygenator according to the present invention.

Figure 5 is a schematic diagram illustrating an exemplary embodiment of an oxygenation assembly including a liquid to liquid oxygenation assembly according to the present invention.

Figure 6 is a schematic diagram illustrating an exemplary embodiment of an extracorporeal circuit including a blood oxygenation system having a liquid to liquid oxygenation assembly according to the present invention.

Figure 7A is a vertical cross-sectional view of an exemplary embodiment of a liquid to liquid oxygenation assembly according to the present invention.

Figure 7B is a top view of the exemplary embodiment of the liquid to liquid oxygenation assembly shown in cross-sectional view in Figure 7A.

Figure 7C is a bottom view of the exemplary embodiment of the liquid to liquid oxygenation assembly shown in cross-sectional view in Figure 7A.

Figure 7D is a partial sectional view of the lower portion of the liquid to liquid oxygenation assembly shown in cross-sectional view in Figure 7A.

Figure 7E is a cross-sectional view taken along line E-E of the lower portion of the liquid to liquid oxygenation assembly shown in cross-sectional view in Figure 7D.

Figure 8 is a partial sectional view of an exemplary embodiment of a catheter assembly for administration of oxygenated blood according to the present invention.

Figure 8A is a cross-sectional view of the exemplary catheter assembly depicted in Figure 8 taken along line A-A.

Figure 8B is a cross-sectional view of the exemplary catheter assembly shown in Figure 8 taken along the line B-B.

Figure 8C is a cross-sectional view of the exemplary catheter assembly shown in Figure 8 taken along the line C-C.

Figure 8D is a cross-sectional view of the exemplary catheter assembly depicted in Figure 8 taken along the D-D line.

Figure 8E is a cross-sectional view of the exemplary catheter assembly depicted in Figure 8 taken along the E-E line.

Figure 8F is an end view of the tip of the exemplary catheter assembly shown in Figure 8.

Figure 9 is a schematic diagram illustrating an exemplary embodiment of an oxygenated blood fluid delivery apparatus according to the present invention.

Figure 10 is a schematic diagram illustrating an exemplary embodiment of a system for supplying a supersaturated fluid with oxygen.

Figure 11 is a schematic diagram illustrating an alternative exemplary embodiment of a system for supplying a supersaturated fluid with oxygen.

Figure 12 is a graph, for an exemplary apparatus for administration of oxygenated blood fluid, of the pressure of the oxygenated blood in the oxygenation assembly as a function of the blood flow rate and the effective inner diameter of the catheter according to the present invention .

Figure 13 is a graph, for an exemplary apparatus for administration of oxygenated blood fluid, of the pressure of the oxygenated blood in the oxygenation assembly as a function of the effective inner diameter of the catheter and the hematocrit according to the present invention.

Figure 14 is a graph, for an exemplary apparatus for administration of oxygenated blood fluid, of the intended oxygenated blood pO2 as a function of the oxygenated fluid pO2 and the systemic pO2 of the patient according to the present invention.

Figure 15 is a graph, for an exemplary apparatus for administering oxygenated blood fluid, of the expected oxygenated blood pO2 as a function of the oxygenated fluid pO2 and the blood flow rate according to the present invention.

Figure 16 is a graph, for exemplary embodiments of a high pressure membrane oxygenator, of the efficiency of the oxygenator as a function of the length of the oxygenator for an exemplary rate of blood flow, according to the present invention.

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 specific forms described. Rather, it is intended to cover all modifications, alternatives and equivalents that fall within the spirit and scope of the invention defined by the appended claims.

Detailed description of specific embodiments

The following description illustrates embodiments of the present invention. For reasons of clarity, not all features of a real implementation of the present invention are described in this specification. It should be appreciated that in connection with the development of any real embodiment of the present invention, many specific application decisions must be made to achieve specific objectives, which may vary from one application to another. In addition, it should be appreciated that such a development effort could be complex and slow, but would remain routine for those skilled in the art who know this description.

For reasons of clarity and convenience, the various embodiments are described herein in the context of cardiovascular intervention applications that generally involve acute or transient ischemia or post-ischemic tissues. However, the present invention may also be useful in other medical applications, such as cancer therapy (e.g., the administration of oxygen-enriched fluids directly to poorly vascularized tumors during radiation treatments or chemotherapy), neurovascular applications (e.g., the treatment of stroke and cerebral trauma patients), lung support in patients with trauma and lung disease, and wound care management.

In addition, although the embodiments can be used to raise oxygen levels, for example, in venous and arterial blood, in blood substitutes, for example, perfluorocarbons, and in their combinations, for reasons of clarity and convenience, reference is made here only to arterial blood.

In addition, the present invention can also be used in connection with medicated fluid infusion therapies to avoid ischemia and / or otherwise improve the effectiveness of the therapies. Examples of medicated fluids used in cardiovascular and neurological procedures that can be infused (before, after or together with oxygenated blood) according to the present invention include, without limitation, vasodilators (eg, nitroglycerin and nitroprusside), platelet activators (by for example, ReoPro and Orbofiban), thrombolytics (for example, t-PA, streptokinase, and urokinase), antiarrhythmics (for example, lidocaine, procainamide), beta blockers (for example, esmolol, inderal), calcium channel blockers ( for example, diltiazem, verapamil), magnesium, inotropic agents (for example, epinephrine, dopamine), perfluorocarbons (for example, fluosol), crystalloids (for example, normal saline, lactated Ringer solutions), colloids (albumin, hespan), products of blood (packed red blood cells, platelets, whole blood), Na + / H + exchange inhibitors, free radical scavengers, diuretics (eg, mannitol), medi antiepileptic caments (for example, phenobarbital, valium), and neuroprotectors (for example, lubeluzole). Medicated fluids can be infused alone or in combination depending on the circumstances involved in a particular application, and they can also be infused with agents other than those specifically listed, such as with adenosine (Adenocard, Adenoscan, Fujisawa), in order to reduce the size of the infarction or effect a desired physiological response.

Turning now to the drawings, a system is provided in which the blood is oxygenated, for example, for administration to a particular predetermined area within the patient's body for the treatment of pathologies such as tissue ischemia and post-ischemic tissues. As schematically shown in Figure 1, one embodiment of such a system includes a blood pump assembly 20 adapted to receive a blood supply from a blood delivery assembly 10. The blood delivery assembly 10 may include a blood supply. blood intended for infusion to a patient or other desired particular position. By way of example, and without limitation, the blood supply can be received from a bag or other blood deposit; of a blood transfer device, such as a cardiac bypass system, blood oxygenator, blood filtration assembly, artificial heart and the like; from other individuals or from the patient.

The pump assembly 20 provides the blood to a blood oxygenation assembly 30. The oxygenation assembly 30 includes an apparatus for raising blood pO2, advantageously to hyperoxemic or hyperbaric levels. In one embodiment, the oxygenation assembly includes a high pressure membrane oxygenator. In another embodiment, the oxygenation assembly includes a liquid to liquid oxygenator.

The oxygenation assembly 30 oxygenates blood received from the pump assembly 20. The oxygenated blood is subsequently supplied to an administration assembly 40 for administration to a desired position. Advantageously, the oxygenation of the blood takes place at least partly at a pressure higher than the atmospheric pressure, and the oxygenated blood is administered with a concomitant pressure drop, so that the formation of clinically significant bubbles is avoided, that is, Oxygenation and blood administration are performed without bubbles.

What constitutes administration without bubbles will vary depending on the circumstances involved in an application

particular. Advantageously, the administration without bubbles will take place with a complete absence of bubbles. However, in some cases of "bubble free" administration, one or more (perhaps even thousands of) clinically non-significant bubbles may be administered, in particular when the gas bubbles include oxygen gas bubbles, which are considered to be more easily accepted by the body than bubbles of other gases. In addition, a clinically acceptable level of bubbles in one application (for example, a coronary procedure) may not be clinically acceptable in another application (for example, a neurological procedure).

We have few written data. However, for cardiological intervention applications, for example, a factor that solves the question of what constitutes a clinically significant bubble may be the total volume of gas, per kilogram of body weight, distributed to the coronary circulation. In cases where the gas is air (as opposed to cases involving oxygen gas bubbles), expert angiographers have attested that a single bubble or multiple bubbles up to approximately 3 mm (3000 μm) in diameter embolize a patient's coronary artery during an angiographic procedure without a resulting clinical problem. The volume of air in a 3 mm diameter bubble is approximately 14 microliters. Thus, this volume of air, embolized as a single bubble in a human coronary artery is benign. In addition, Khan et al. (1995) Coronary Air Embolism: Incidence, Severity, and Suggested Approaches to Treatement, Catheterization and Cardiovascular Diagnosis 36: 313-18, retrospectively studied 3715 coronary angiograms to determine the incidence and severity of coronary air embolism, and clinical severity related to bubble volume as follows: minimal (several bubbles that disappear immediately without symptoms); soft (1 ml of air with mild transient symptoms); moderate (2-3 ml of air usually associated with severe symptoms); and massive (> 3-5 ml of air associated with serious life-threatening complications). The mild clinical effect observed with 1 ml of air in the study is approximately equivalent to experiencing a single bubble with a diameter of 12 mm, since the volume of this bubble is 1 ml. Thus, it seems that an air bubble of 3 mm in diameter is clinically insignificant: it is a minimum volume of air per unit of body weight.

Accordingly, for a coronary application in which the bubbles of primary interest are oxygen bubbles, a total volume of gas administered of less than about 1-2 ml is considered to represent clinical insignificance. However, since oxygen is consumed metabolically, an infusion of oxygen bubbles is not considered as traumatic as the infusion of inert gases (eg nitrogen).

Turning now to Figure 2, an exemplary oxygenation assembly is schematically illustrated including a high pressure membrane oxygenator assembly 50. The membrane oxygenator assembly 50 includes a membrane 52 that effectively divides the assembly 50 into two separate fluid compartments: a gas side compartment 54 and a blood side compartment 56. The oxygen gas from an oxygen gas supply assembly 58 is supplied into the compartment 54 at a pressure P1. Advantageously, the assembly 58 is a regulated oxygen bottle and the pressure P1 is a pressure higher than atmospheric and less than about 30 psia. Very advantageously, the pressure P1 is approximately 2 atmospheres. The blood to be oxygenated is supplied by a blood delivery assembly 60 into the compartment 56 at a pressure P2. Advantageously, the pressure P2 is greater than about P1, and mass flow of gas through the membrane 52 is avoided.

When the oxygen gas is provided to the compartment 54 and the blood provided by the blood delivery assembly 60 flows through the compartment 56, oxygen is diffused through the membrane 52 to oxygenate the blood. The oxygenated blood leaves the compartment 56 via a line 62, for example, for administration by a catheter to the patient's body.

In an alternative embodiment the membrane oxygenator assembly is provided with a gas outlet hole 64, so that gas can flow through the compartment 54 when the outlet hole 64 is open. Advantageously, the outlet hole 64 includes an adjustable valve or other operable means for controlling the rate of gas flow through the compartment 54 for a given pressure P1. The fluid stream leaving compartment 54 may be vented to the atmosphere or to suitable means to process and discard the outlet fluid. Depending on the circumstances involved in a particular application, gases may be diffused through the membrane 52 of the blood flowing through the compartment 56 to join the current leaving the compartment 54.

The shape that the membrane oxygenator assembly 50 can take, and its exact size and shape, may vary depending on the circumstances involved in a particular application. By way of example only, and without limitation of the scope of the present invention, the membrane oxygenator assembly 50 may include an external flow fiber beam oxygenator in which compartment 54 includes a plurality of hollow fibers through which gas can flow; compartment 56 includes a housing or container surrounding the hollow fibers and into which the blood supplied inside the housing or container can contact the outer surface of the hollow fibers; and the membrane 52 includes the total active surface area of the hollow fibers through which oxygen diffuses when blood is supplied inside the housing or container and oxygen gas is supplied inside the hollow fibers.

In an alternative embodiment (see Figure 3), the high pressure membrane oxygenator includes a blood oxygenator assembly of the hollow fiber type and internal flow. Advantageously, the assembly includes a housing assembly of generally cylindrical shape loosely packaged with a plurality of hollow fibers 70. The housing advantageously includes a generally tubular main body portion 72 having first and second ends; and end caps 74, 76 fixedly connected (eg, with UV adhesive) to the first and second ends, respectively. The ends of the hollow fibers 70 are advantageously fixed within the housing assembly by an encapsulating material, for example, a polyurethane resin. Advantageously, the encapsulating material forms fluid barriers 78, 80 near the first and second ends, respectively. The hollow fibers 70 extend through the barriers 78, 80, so that the housing assembly includes four regions of fluid flow within the housing assembly: a blood inlet manifold 82, including the fluid space defined by barrier 78 and cap 74; a blood outlet manifold 84, including the fluid space defined by barrier 80 and plug 76; an oxygen chamber 86, including the fluid space defined by the barriers 78, 80, the housing body portion 72, and the outer surfaces of the hollow fibers 70; and the interior of hollow fibers 70, a region that includes a plurality of continuous fluid paths between the blood inlet and outlet manifolds 82, 84.

Advantageously, the end cap 74 includes a blood inlet port 88, and the cap 74 is provided with a luer connector 92 for detachably attaching the oxygenator assembly to an apparatus to provide a supply of blood to be oxygenated. The end cap 76 includes a blood outlet port 90, and the cap 76 is provided with a luer connector 94 for detachably attaching the oxygenator assembly to an oxygenated blood delivery apparatus, for example, a tube and catheter or wire of Infusion guide The housing body portion 72 includes gas inlet and outlet holes 96, 98, respectively. The gas inlet port 96 is advantageously provided with a luer connector 100 for detachably coupling the oxygenator assembly to an oxygen gas supply assembly. The gas outlet orifice 98 is advantageously provided with a luer connector 102 for detachably coupling the oxygenator assembly to an apparatus for venting the gas stream leaving the oxygenator assembly to the atmosphere or to a filter assembly before disposal.

Thus, a method is provided in which oxygen is supplied to the oxygen chamber 86 at a pressure higher than atmospheric. The blood enters the blood inlet manifold 82 through the hole 88 and advances through the hollow fibers 70 where oxygenation of the blood takes place by virtue of the diffusion of oxygen through the fibers 70. The gas transfer Massive is avoided by keeping the blood pressure above the gas pressure. The oxygenated blood then leaves the oxygenator assembly through the blood outlet manifold 84 and the hole 90 for administration to a given position.

The hollow fibers 70 advantageously include a 160 cm stretch of matted fibers (each fiber is advantageously approximately 8-10 cm in length) loosely wound in a cylindrical shape, so that a gap of approximately 0.05 inch between the outside diameter remains of the fiber roll and the inner diameter of the oxygenator housing. The ends of the fibers near the inlet and outlet manifolds are advantageously open and clean. An especially advantageous tangled fiber commercially available for use is the Akzo OxyphanTM fiber mat, a hollow polypropylene fiber mat including 16.8 fibers / cm, each fiber having a wall thickness of approximately 50 μm and an interior diameter of 280 μm, which can be obtained from Akzo Nobel, Germany.

For a given pO2 of inlet blood and a specified pressure of oxygen on the gas side of the membrane, as well as a specified rate of blood flow and a fiber housing diameter, the length of the membrane oxygenator can be determined to ensure balance oxygen saturation. Naturally, many variations are possible. By way of example only, and without limitation, a unit having a diameter of approximately 4 cm and a length of approximately 10 cm, with a void volume of approximately 0.4 for fibers of approximately 380 μm outside diameter and approximately 280 μm inside diameter, it is sufficient to achieve equilibrium saturation for a blood flow rate of approximately 200 ml / minute. Such a device would have a total volume of priming blood of approximately 41 ml. Naturally, lower blood flow rates, smaller diameter fibers, tighter packing of the fibers, and an increase in oxygen pressure will reduce the necessary size of the device, which is independent of the desired blood pO2. In any case, the broad characterization of the mass transfer coefficients that is typically required for membrane and external flow blood oxygenators is unnecessary, and smaller priming volumes can be achieved.

In one embodiment, an approximation of the transfer of oxygen to the blood can be obtained using a model based on the convective diffusion equation that considers the flow of blood through a circular tube as a variant of the Graetz mass transfer problem -Nusselt-Leveque for diffusion of solute through the walls of a tube in which the solvent experiences laminar flow of Hagen-Poiseuille. Under this model, for oxygen supplied through the tube walls at a partial pressure equal to the oxygen gas pressure supplied to the oxygenator, as shown by way of example in Figure 16, the size of the oxygenator can be determined by application to the model of several variables (for example, blood flow rate, oxygen solubility, the number and / or size of the fibers, diffusivity of the oxygen in the blood, etc). For a maximum desired rate of blood flow Qmax, the size of the oxygenator is advantageously minimized by

so that a desired efficiency β can be achieved, where β is the ratio of the output blood pO2 pO2 (out) and the oxygen gas pressure. As depicted in Figure 16, for a blood flow rate of 75 ml / minute with an oxygenator including 4100 fibers of 280 μm internal diameter, an oxygenator length of approximately 6 cm or more results in an efficiency β = one.

Other models can also be used to determine oxygen transfer, for example, models based on empirical evidence of mass transfer coefficients, or mass transfer models adapted to specific applications that involve other mass transfer limit conditions, geometries of flow, fluids, operating parameters, etc. Advantageously, the oxygen transfer model can be used to characterize an oxygenator in order to promote its selection by a caregiver for a particular application. In one embodiment, a method is provided including the steps of using an oxygen transfer model to characterize an oxygenator assembly in order to promote the selection of the device for an application in which oxygenated blood is to be administered to the patient at a rate of desired flow and pO2. More advantageously, oxygenated blood is supplied at a level of pO2 greater than about 760 mm Hg.

Since the device can be advantageously designed for equilibrium mass transfer, equilibrium heat transfer can also take place. Thus, a system requirement may include means to control the temperature of the blood leaving the assembly. By way of example, a simple heating device could include, for example, an electric blanket wrapped around the oxygenator unit, with feedback control, to maintain the blood temperature at approximately 37 ° C.

Turning to Figure 4, an extracorporeal circuit for oxygenating blood is shown including a high pressure membrane oxygenator 110. System requirements may include a blood pump assembly 112 and an oxygen gas supply assembly 114 operatively coupled to the oxygenator. High pressure membrane 110. Other components may include blood temperature control devices, bubble detection apparatus, pressure / temperature sensors, pO2 sensors, etc. (not shown in Figure 4). Advantageously, the various system components are operatively coupled to a processing and control assembly 116 including electronic circuitry to allow the sending and receiving of signal inputs and / or control orders between one or more of the various system components. A display assembly 118 coupled to the processing and control assembly 116 may serve as a separate user interface for data entry and / or process control orders and / or for displaying system status and / or processing outputs .

The flow characteristics of the oxygenated blood leaving the membrane oxygenator assembly 110 will depend on the circumstances surrounding the particular application involved. Typically, for example, the supply of oxygenated blood provided to a catheter for infusion to the patient's body will be a controlled flow defined by the flow parameters selected by the caregiver. In an application that involves the subselective administration of oxygenated blood for the treatment of ischemic tissues and / or the prevention of ischemia, flow rates of approximately 75-100 ml / minute may be advantageous. Again, the factors that influence the determination of blood flow characteristics may include one or more of the many clinical parameters.

or variables of the oxygenated blood to be supplied to the catheter or administered to the patient, for example, the size of the patient, the percentage of general circulation to be provided, the size of the blood vessel to be accessed, hemolysis, hemodilution, pO2, pulsatility, flow rate mass, volumetric flow rate, temperature, hemoglobin concentration and pH.

Turning to Figure 5, an alternative embodiment of an oxygenation assembly including a liquid to liquid oxygenation assembly 200 is schematically depicted. The assembly 200 advantageously combines a supply of supersaturated fluid with oxygen received from a supply assembly 210 with a supply of blood received from a supply assembly 220 to form oxygenated blood for administration to a given position.

In one embodiment, the supersaturated oxygen fluid advantageously includes a volume of standardized dissolved oxygen at a standard temperature and pressure of between about 0.5 and about 3 times the volume of the solvent. The fluid can be supplied to the system at a pressure between about 100 psi and about 5000 psi, more advantageously between about 100 psi and 600 psi, although the exact pressure may vary depending on the circumstances involved in a particular application. In addition, the supersaturated fluid supplied with oxygen can be sterile and have an administration path that does not include gas

or superficial places where potentially clinically significant bubbles can nuclear and / or grow.

As described herein, a preferred fluid for use according to the present invention is a supersaturated oxygen fluid. However, other supersaturated fluids with gas may 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, nitrous oxide, carbon dioxide and air.

Exemplary apparatus and methods for the preparation and administration of supersaturated oxygen fluids are described in US Patent No. 5,407,426 to Spears entitled "Method and apparatus for administering oxygen to blood"; US Patent No. 5,569,180 to Spears entitled "Method for administering a supersaturated fluid with gas to a place of spent gas and its use"; U.S. Patent No. 5,599,296

Spears entitled "Apparatus and method of administration of supersaturated liquids with gas"; and US Patent No. 5,893,838 to Daoud et al. entitled "System and method for high pressure administration of supersaturated fluids with gas", which are incorporated herein by reference. In addition, the description concerning exemplary apparatus and methods for the preparation and / or use of supersaturated fluids with gas, including, for example, supersaturated fluids with oxygen, in various applications, can be found in the following patents and patent applications, which are incorporated herein by reference: United States Patent Application, in process, serial number 08 / 581,019, filed on January 3, 1996, which is a partial continuation of United States Patent Application serial number 273,652, filed on July 12, 1994, now U.S. Patent No. 5,569,180, which is a partial continuation of U.S. Patent Application Serial Number 152,589, filed on November 15, 1993, now U.S. Patent No. 5,407 .426, which is a partial continuation of U.S. Patent Application Serial Number 818,045, filed on January 8, 1992, now U.S. Patent No. number 5,261,875, which is a continuation of US Patent Application US Serial No. 655,078, filed Feb. 14, 1991, now US Patent 5,086,620 number.

In an alternative embodiment (see Figure 10), the supersaturated oxygen fluid supply assembly includes an apparatus including a chamber 300 coupled to a regulated source of oxygen gas 310 that maintains a desired pressure in chamber 300. Advantageously, the volume of the chamber is approximately 100 ml, and the pressure in the chamber 300 is approximately 600 psi a physiological fluid (eg, saline) enters the chamber 300 through a nozzle 320. The nozzle 320 advantageously forms droplets of fluid at that oxygen is diffused when the droplets advance into the chamber 300. More advantageously, the nozzle 320 includes an atomizing nozzle adapted to form a droplet cone 330 definable by an included angle α, which is advantageously about 20 to about 40 degrees at pressures operating conditions (for example, approximately 600 psi) for a pressure drop through the nozzle 320 of more than apr approximately 15 psi. The nozzle 320 is a pressurized, swirling, single-type atomizing nozzle, including a fluid orifice of approximately 100 μm in diameter. Advantageously, the nozzle 320 forms fine droplets of fluid of less than about 100 µm in diameter, and more advantageously of about 25 µm. The fluid is advantageously supplied to the chamber 300 by a pump 340 operatively coupled to a fluid supply assembly 350. The fluid is advantageously supplied at a controlled rate based on the desired flow rate of fluid supersaturated with oxygen. In the lower part of the chamber 300 fluid is collected forming a bath 360 that advantageously includes fluid having a volume of standardized dissolved gas at a standard temperature and pressure of between about 0.5 and about 3 times the volume of the solvent. The fluid is removed from the chamber 300 (for example, by means of a pump 370, which advantageously allows control of the flow rate, or by virtue of the pressure in the chamber 300) for administration to a given position (for example, a a set of blood oxygenation).

More advantageously, as shown in Figure 11, the supersaturated oxygen fluid is produced by atomizing a physiological liquid such as saline provided from a supply assembly 400 to a pressurized chamber 410 at approximately 600 psi by oxygen. The oxygen is advantageously supplied to the chamber 410 from an oxygen supply assembly 412, for example, a medical grade bottle E.

Saline is advantageously supplied to chamber 410 (for example, from a saline bag or other reservoir) by the nozzle 411 by a piston-shaped assembly including a syringe pump 416 capable of continuously administering 600+ psi of saline or intermittently depending on the circumstances involved in a particular application. Syringe pump 416 advantageously includes a piston 418 operatively coupled to a motor assembly 420. A check valve 422 prevents unwanted loss of fluid from line 413 during filling of syringe pump 416. A check valve 424 prevents unwanted flow of saline to the fluid supply assembly 400 when fluid comes out of the syringe pump 416. Advantageously, the syringe pump 416 includes a fluid reservoir having a volume of about 10 to about 100 ml, although pumps may be used of different size syringe depending on the circumstances involved in a particular application. In addition, the chamber inlet is advantageously filtered to protect it from any residue that could be present in the pumping system.

Three needle valves 426, 428, 430 are advantageously used to control the flow of fluid to and from chamber 410. Table II describes the modes of operation of the needles. During normal operation, the pumping system is turned off and only the administration valve (needle 430) is open to allow fluid administration of chamber 410 by means of fluid outlet lumen 401 and outlet of assembly 402, for example , to a set of blood oxygenation. When the chamber must be filled (for example, in response to a sensor signal indicating that the fluid level in the chamber has fallen to a predetermined level), a filling sequence is advantageously initiated in two parts. In the first part of the filling sequence, the pumping system is activated and the dilution flow is activated, that is, the dilution valve (needle 426) is open to allow the administration of fluid from line 413 to the chamber 410 via line 403. In the second part, needle 426 is closed, and the flow is directed from line 413 through atomizing nozzle 411 via line 405. The administration valve (needle 430) remains open for both parts of the filling sequence. By varying the time of each part of the filling sequence, the concentration of the fluid in the chamber can be varied. For example, to achieve a concentration of 300 psi in a pressurized chamber at 600 psi, during a time of

Total filling of 40 seconds each part of the two-part filling sequence will last approximately 20 seconds. The check valve 434 prevents backflow of the chamber through the atomizing nozzle to the pumping system when the pumping system reservoir is filling. Advantageously, check valve 434 includes a ball that seats under pressure against a portion of the valve body to prevent unwanted reflux of fluid. In addition, in order to put the chamber in bypass, that is, so that the fluid neither enters nor leaves the chamber, a washing sequence is initiated. During washing, the delivery valve (needle 430) and the dilution valve (needle 426) are closed, the wash valve (needle 428) is open, and the pumping system is activated, so that non-oxygenated saline passes Through the system.

Table II

Pump status

Valve status

426 needle

428 needle 430 needle

Normal operation

disabled Closed Closed Open

Filling sequence

(Part 1) Activated Open Closed Open

(Part 2)

Activated Closed Closed Open

Wash sequence

Activated Closed Open Closed

Advantageously, each of the needles 426, 428, 430 is opened or closed independently or in conjunction with the opening and closing of one or more needles, to achieve a desired flow of supersaturated fluid with oxygen from the assembly. The actuator assembly 432 may include switching means, for example, solenoids, operatively coupled to each valve to move the valves between open and closed positions.

The chamber 410 advantageously includes a disposable housing 415 and plug 417 attached (for example, by threaded coupling) or fixedly connected (for example, by UV adhesive) in order to define the interior space in which saline and oxygen are introduced. The chamber 410 may further include a bacterial filter assembly 414 for removing unwanted particulates from the gas entering the chamber 410. The housing 415 and the cap 417 may be formed of polycarbonate or other suitable biocompatible material.

For security, the chamber 410 may be arranged at least in part within a protective housing assembly 438, including, for example, a stainless steel bracket. In one embodiment, a block 419 can be placed inside the support 438 on top of the chamber 410. Advantageously, the block 419 is provided with a recess or lower surface portion generally concave, so that an impending gas chamber 421 is defined by the lower surface of the block 419 and the upper end or surface of the chamber 410. Advantageously, the boundary between the block 419 and the chamber 410 is sealed (for example, with an O-ring, seal or other sealing means). A ring 423 in threaded engagement with the support 438 can help retain the sealed block 419 and place it against the chamber 410 when oxygen gas is introduced from the supply assembly 412 into the impeller chamber 421 through a gas inlet hole in the block 419. From the impending chamber 421, gas can enter the chamber 410 through the filter 414 disposed along a hole through the plug 417. Advantageously, the gas pressures inside the impellent chamber 421 and the chamber 410 are approximately equal.

Advantageously, the chamber 410 and other system components include one or more sensors, for example, fluid level sensors, pressure transducers, etc. (not shown in Figure 11) in order to be able to monitor the state of the system during operation. Advantageously, the sensors and various system components are coupled to a processing and control assembly 436 including electronic circuitry to allow the sending and reception of signal inputs and / or control orders between one or more of the various system components. A display assembly 440 coupled to the processing and control assembly 436 can serve as a separate user interface for data entry and / or process control orders and / or for displaying system status and / or processing outputs .

For reasons of clarity and convenience, the fluid supply assemblies supersaturated with oxygen such as those depicted in Figures 10 and 11 have been described including liquid atomizer assemblies. However, other means can be used to contact the liquid and gas. For example, in some cases it may be desirable to arrange the liquid inside the pressurized chamber as a thin film in contact with oxygen gas. The liquid film can be created, for example, by sheets, sieves, screens or other mechanical means or arranged inside or as part of the chamber. In addition, fluid supply assemblies other than the syringe pump and pump embodiments, valve devices, and / or liquid flow paths represented in combination with the various other components described herein can be used.

Turning now to Figure 6, an extracorporeal blood oxygenation circuit is depicted including a pump assembly 500 operable to distribute blood withdrawn from a patient to an oxygenation assembly

liquid-to-liquid sample 600. The assembly 600, of which portions are shown in more detail in Figures 7A-E, advantageously includes an injector housing 610, a side wall assembly 620, and a plug 630 attached in order to define an interior space 612 within which the blood provided by the supply tube 640 is mixed with supersaturated fluid with oxygen provided by the capillary assembly 650 to form oxygenated blood. The oxygenated blood leaves the inner space 612 through the outlet 614 for administration by the return tube 660 to a fluid delivery apparatus 510. The injector housing 610, the side wall assembly 620, the plug 630, and other components of the together they are advantageously disposable and are made of biocompatible materials, for example, polycarbonate, polyethylene and the like. The tubes advantageously include medical grade PVC pipes.

The blood supply tube 640, which may include a pressure monitoring orifice 642, advantageously includes a continuous blood flow path between a first tube end operatively coupled to the output of the blood pump assembly 500 and a second end of tube fixedly connected to the injector housing 610 and in fluid communication with the inner space 612, for example, by a fluid passage 644 that extends through at least a portion of the housing 610 and including a fluid hole 646. Advantageously, the blood flows through the hole 646 creating a vortex or cyclonic flow within the interior space 612, for example, along a substantially tangential path to the chamber wall.

The capillary assembly 650 advantageously includes a single fused silica capillary having an inner diameter of 100 µm and an outer diameter of 350 µm, which includes a continuous fluid path between a first end of the assembly 650 operatively coupled to the outlet of a set of supply of supersaturated fluid with oxygen 550 and a second end of the assembly 650 arranged to allow fluid to escape from the capillary entering the inner space 612 of the liquid to liquid oxygenator. Advantageously, the capillary assembly 650 includes between its first and second ends a luer adapter 652 for fixing the capillary in position after being placed within a lumen 654 that passes through at least a portion of the injector housing 610 to the interior space 612. The capillary assembly may also advantageously include a support assembly (for example, a rigid tube within which at least a portion of the capillary is disposed) near the second end of the assembly 650 to help keep the capillary fluid outlet orifice in position. within the interior space 612, and / or a deformation relief assembly (for example, a flexible tube within which at least a portion of the capillary is disposed) to help avoid excessive bending or capillary cocas.

Alternatively, the capillary assembly 650 may include a plurality of capillaries having internal diameters in the range of about 20 to about 1000 µm, with an inside diameter of about 100 µm to about 125 µm being especially advantageous. The capillaries are advantageously encapsulated together

or otherwise join on their outer surfaces to form a single capillary beam. Capillaries can also be formed from glass, PEEK (polyether ether ether ketone) or other biocompatible material. Treatment of capillaries with a water-wettable coating or liquid rinse before use may be advantageous to help ensure that the inner capillary surface (s) do not promote the formation of bubbles clinically. significant.

Advantageously, the interior space 612 is pressurizable, so that during the operation a blood supply is accumulated in the lower part and a gas load in the upper part of the liquid to liquid oxygenation assembly. The plug 630 may be provided with a hole 632 to be able to monitor the pressure within the interior space 612. The assembly may also include one or more fluid sample holes, for example, the hole 634 in the return tube 660.

The flow characteristics of the oxygenated blood leaving the liquid to liquid oxygenation assembly 600 will depend on the circumstances surrounding the particular application involved. Typically, for example, the supply of oxygenated blood provided to a catheter for infusion to the patient's body will be a controlled flow defined by the flow parameters selected by the caregiver. In an application that involves the sub-selective administration of oxygenated blood for the treatment of ischemic myocardial tissues and / or the prevention of myocardial ischemia, flow rates of approximately 75-100 ml / minute may be advantageous. Again, factors that influence the determination of blood flow characteristics may include one or more of the many clinical or variable parameters of the oxygenated blood to be delivered to the catheter or administered to the patient, for example, the size of the patient, the percentage of general circulation to be provided, hemolysis, hemodilution, pO2, pulsatility, mass flow rate, volumetric flow rate, temperature, desired blood vessel, hemoglobin concentration and pH.

It is possible to make an approximation of the pO2 of the oxygenated blood leaving the liquid to liquid oxygenation assembly 600 for a particular application. Advantageously, the processing and control assembly includes a computer, electronic circuitry, and / or processing software embedded within the electronic circuitry (for example, programmed electronic chips) that continuously executes an approximation model of pO2 during the operation of the system that takes into account and corrects if possible variations of pO2 resulting from variables such as temperature, pH, Base excess (BE), pCO2, P50, hemoglobin-oxygen saturation levels, etc. The processing and control set advantageously displays the model results (for example, expected pO2) for the caregiver in the display set together with one or more of the values entered, detected, calculated or obtained.

otherwise of the variables related to the model.

For example, an approximation model of pO2 can be advantageously based on the Severinghaus equation. See Severinghaus, J. W., Simple, Accurate Equations for Human Blood O2 Dissociation Computations, Journal of Applied Physiology 46 (3): 599-602. Advantageously, the pO2 values of the oxygenated fluid and the oxygen concentration are regulated to correct any difference between the temperature of the oxygenated fluid that enters the liquid to liquid oxygenation assembly and the temperature of the oxygenated blood to be infused. Hemoglobin-oxygen saturation is calculated to estimate the amount, if any, of oxygen in the oxygenated fluid that will bind to hemoglobin before increasing plasma oxygen levels. The difference between the initial oxygen content of the patient's blood and the calculated oxygen content that would achieve a hemoglobin saturation of 100% represents the amount of oxygen that will bind to the hemoglobin before plasma elevation of pO2. By calculating the concentration of the oxygenated fluid distributed to the circulating blood, and then adjusting said amount down by an amount equal to the amount of oxygen that will bind to hemoglobin before the elevation of plasma pO2, the expected pO2 can be obtained by combining the adjusted concentration of oxygenated fluid with the initial pO2 of the patient.

The expected expected pO2 values obtained using an approximation model based on the Severinghaus equation are set forth in Figures 14 and 15. Figure 14 represents the predicted pO2 as a function of the oxygen fluid pO2 and the patient's systemic pO2. Figure 15 represents the predicted pO2 as a function of the oxygenated fluid pO2 and the blood flow rate. Depending on the circumstances involved in a particular application, other approximations of the pO2 model may be advantageously used. Such model approaches can be based, for example, on other equations and / or methods for determining pO2, such as those described in Sharan, M., Singh, MP, Aminataei, A. (1989) to the Model for the Computation of the Oxygen Dissociation Curve in Human Blood, Biosystems 22 (3): 249-60; and Siggard-Anderson, O., Wimberley, PD, Gothgen, I., Siggard-Anderson, M. (1984) a Model of the Hemoglobin-Oxygen Dissociation Curve of Human Blood and of Oxygen Partial Pressure as a Function of Temperature, Clin . Chem. 30 (10): 1646-51.

The administration apparatus 510 may include any clinically acceptable fluid delivery device such as a catheter (eg, quick swap, cable, etc.), infusion guide wire, sheath and the like. By way of example only, as shown in Figures 8 and 8A-F, such an administration device includes a catheter 700 including a proximal end 710 adapted to couple at the outlet of an oxygenation assembly (see, for example, the assemblies represented in figures 4 and 6) and a distal end 720 removably insertable within the patient's body. Catheter 700 includes a relatively rigid proximal portion 730, to provide pushing and torsion, a relatively flexible distal portion 740, which provides a balance of stiffness and flexibility to track the vasculature, and a transition portion 750 of intermediate relative stiffness and flexibility. The catheter 700 includes a generally tubular element having a central lumen 760 forming a continuous fluid path between the ends 710, 720. The distal portion 740 of the catheter 700 advantageously includes a second lumen 780 through at least a portion of its length . The second lumen 780 advantageously includes a guide wire lumen of approximately 0.017 inch of internal diameter and of sufficient length to promote catheter tracking on a 0.014 inch guide wire inserted through lumen 780, and to allow rapid exchange of the catheter without the use of extension wires. A lumen 780 of approximately 4 cm in length, a distal portion 740 of approximately 5 cm in length, and a general catheter of approximately 140 cm in length may be advantageous, in particular for applications involving sub-selective administration of oxygenated blood.

Fluid may advantageously flow out of the central lumen 760 through an end hole located at the distal tip of the catheter 700 and / or through one or more side holes 790 arranged along the distal portion 740. Advantageously, the side holes 790 they are located along the portion of the catheter that extends back approximately 0.5 inches from the distal tip, with sequential side holes advantageously spaced so that the axes passing through the side holes are generally perpendicular to the central axis of the catheter and approximately parallel to the inclined axes circumferentially offset from each other approximately 90 degrees (compare, for example, Figures 8D and 8E). The fluid lumen can be of any shape, for example, D-shape, kidney shape, round, oval, square, etc.

Catheter 700 may include one or more radiopaque marker bands 800 to help the caregiver position the device. The distal end of catheter 720 may also include an atraumatic tip, advantageously of 80 shore hardness, to promote ease of placement without promoting clinically significant damage to vascular tissues. The proximal axis has advantageously greater shore hardness than the distal axis to provide pushability. By way of example, the proximal portion 730 of the catheter may include an outer diameter of 5 Fr, an inner diameter of 3.6 Fr and make of a 70 shore V material; and the distal portion 740 may include an outside diameter of 3.8 Fr, an inside diameter of the fluid lumen 760 of 2.3 Fr and be made of a D 55 shore material. Materials used to make catheter 700 may include polyethylene or any other suitable biocompatible material (eg, polyurethane, polyamide, polyester, elastomers, PET, thermoplastics, etc.).

Turning to Figure 9, an oxygenated fluid delivery apparatus advantageously includes a blood pump assembly 900; a first length of tubes 910 between the pump assembly 900 and a set of

blood oxygenation 920; a second length of tubes 930 between the blood oxygenation assembly 920 and an administration assembly 940; and the administration set 940. As shown in Figure 9, the administration set 940 includes a proximal portion 950, an intermediate portion 960, and a distal portion

970. Advantageously, the fluid delivery apparatus includes a continuous flow of fluid between the blood pump assembly 900 and the distal tip 980 of the administration assembly 940.

As depicted in Figure 9, the intermediate portion 960 may include a relatively short segment (eg, approximately 1 cm in length) that narrows in the proximal portion 950 to meet the distal portion 970. In alternative embodiments, the Intermediate portion may include a transition segment of greater length including one or more end-to-end joined portions, each portion including an inner lumen of fluid through which oxygenated blood can flow. By varying the size, shape and materials of the various catheter portions and lumens of oxygenated blood fluid, a catheter having an effective diameter, handling characteristics, etc., desired for a particular desired application can be obtained. In addition, by varying the size and length of the 930 tube, and / or including flow restrictors and / or other assemblies that affect the pressure drop along the route of administration of oxygenated blood (eg, a pressure cuff) , a fluid delivery apparatus (which in some cases can be characterized in terms of a general effective diameter of the path of oxygenated blood fluid) can be obtained to achieve a desired range of oxygenated blood pO2 for a particular application.

By way of example, for an exemplary apparatus for administering oxygenated blood fluid including a 1.4 m long catheter coupled at its end close to a 3 m oxygenated blood return tube having an inside diameter of 0.094 inch, The pressure of the oxygenated blood in the oxygenation assembly 920 is shown in Figure 12 as a function of the blood flow rate and the effective diameter of the catheter for an exemplary application that involves the administration of oxygenated blood to a patient having a mean arterial pressure of 100 mm Hg and a hematocrit of 38%, and is represented in Figure 13 as a function of the effective internal diameter of the catheter and hematocrit for an exemplary application that involves the administration of oxygenated blood at 75 ml / minute to a patient which has an average blood pressure of 100 mm Hg. As shown in Figures 12 and 13, for a constant rate of blood flow Qsangre, as the effective inner diameter of the catheter increases, the pressure of the Pluid blood (gauge) in the oxygenation assembly 920 decreases.

Knowing the simplified and approximate ratio of administration without bubbles, ΔPfluid> pO2 (out), a caregiver who has a catheter characterized by an effective inner diameter can use a graph such as Figure 12 to determine if an appropriate range of rates can be achieved blood flow if the caregiver used a fluid delivery device including the catheter to deliver blood that has a desired pO2. Alternatively, a caregiver who specifies a desired oxygenated blood pO2 and a range of oxygenated blood flow rates may use a graph analogous to that depicted in Figure 12 to help select a catheter for use in a fluid delivery apparatus for a particular application Likewise, other graphs (eg, figure 13) may be used by the caregiver or others in other applications to facilitate the provision of an oxygenated blood fluid delivery apparatus.

The present invention has been described in terms of exemplary embodiments. According to the present invention, the operating parameters of the system can be varied, typically by specifying them and selecting a doctor or caregiver for the desired clinical indication. Furthermore, it is contemplated that other embodiments, which can easily be devised by persons of ordinary skill in the art based on the ideas set forth herein, may fall within the scope of the invention defined by the appended claims. The present invention can be modified and put into practice in different, but equivalent, ways that will be apparent to those skilled in the art who know the ideas set forth herein.

No limitations on the details or construction or design shown herein are provided, except as described in the appended claims. Thus, it should be clear that the specific embodiments described above can be altered and modified, provided that such variations and modifications fall within the scope of the present invention set forth in the appended claims.

Claims (15)

1. A device to oxygenate blood and administer oxygenated blood to a patient, including the device: a blood pump assembly (20) coupled to a blood supply (10); a blood oxygenation assembly (30) coupled to the blood pump assembly (20), receiving the blood oxygenation assembly (30) the blood from the blood pump assembly (20) and oxygenating the blood; an administration system (40) coupled to the blood oxygenation assembly (30), the administration system (40) being adapted to administer the oxygenated blood to a patient, including the administration system (40): a generally tubular elongate element (700) having a proximal end portion (710) and a distal end portion (720), the distal end portion (720) being adapted to be inserted into the patient and the end portion being coupled next (710) to the blood oxygenation assembly (30), the element (700) also having a first lumen (760) for transporting the oxygenated blood that generally extends from the proximal end portion (710) to the portion of distal end (720), and the element (700) having a transition portion (750) located between the proximal end portion (710) and the distal end portion (720), characterized in that the transition portion (750) is relatively flexible compared to the proximal end portion (710) and is relatively rigid compared to the distal end portion (720).

2.

 The device set forth in claim 1, including at least one hole (790) located in a peripheral wall of the element (700) and extending to the first lumen (760).

3.

 The device set forth in claim 2, wherein the at least one hole (790) is formed in the distal end portion (720) of the element (700).

Four.

 The device set forth in claim 1, including a plurality of holes (790) located in a peripheral wall of the element (700) and extending to the first lumen (760).

5.

 The device set forth in claim 4, wherein the plurality of holes (790) are formed in the distal end portion (720) of the element (700).

6.

 The device set forth in claim 4, wherein each of the plurality of holes (790) includes a passing axis, each passing axis being generally perpendicular to a longitudinal axis of the element (700) and being circumferentially offset from each passing axis. adjacent.

7.

 The device set forth in claim 1, including a second lumen (780) that extends along at least a portion of the element (700).

8.

 The device set forth in claim 7, wherein the second lumen (780) is sized and positioned to promote tracking of the element (700) on a guidewire.

9.

 The device set forth in claim 1, including a radiopaque marker located in the element (700).

10.

 A device for oxygenating blood and administering oxygenated blood to a patient, according to one or several preceding claims, further including the device:

a plurality of holes (790) formed in a peripheral wall of the element (700) and extending to the first lumen (760), the multiple holes (790) being located in the distal end portion (720) of the element (700) , each of the plurality of holes (790) having a passing axis, each passing axis being generally perpendicular to the longitudinal axis of the element (700) and being circumferentially offset from each adjacent passing axis.

eleven.

 The device set forth in claim 10, wherein each passing axis is circumferentially offset 90 degrees from each adjacent passing axis.

12.

 The device set forth in claim 10, wherein the plurality of holes (790) are spaced at least 0.5 inches from the distal end (720) of the element (700).

13.

 The device set forth in claim 10, wherein the plurality of holes (790) are sequentially spaced along the longitudinal axis.

14. The device set forth in claim 10, wherein the first lumen (760) ends at an open distal end. (720) of the element (700). 15. The device set forth in claim 10, wherein the first lumen (760) ends at a closed distal end. (720) of the element (700). 10 16. A device for oxygenating blood and administering oxygenated blood to a patient according to one or several preceding claims, further including the device: a plurality of holes (790) formed in a peripheral wall of the element (700) and extending to the first 15 lumen (760), the multiple holes (790) being located in the distal end portion (720) of the element (700), each of the plurality of holes (790) having a passing axis, each passing axis being generally perpendicular to the longitudinal axis of the element (700) and being circumferentially offset from each adjacent axis of passage.