WO2015164629A1

WO2015164629A1 - Catheter for portable lung assist device

Info

Publication number: WO2015164629A1
Application number: PCT/US2015/027334
Authority: WO
Inventors: Abbas ARDEHALI
Original assignee: The Regents Of The University Of California; U.S. Department Of Veterans Affairs Office Of The General Counsel
Priority date: 2014-04-24
Filing date: 2015-04-23
Publication date: 2015-10-29
Also published as: EP3134160A1; EP3134160A4

Abstract

The present invention relates to a catheter for use with a lung assist device that minimizes or eliminates the recirculation of oxygenated blood. The catheter of the present invention can be used to drain blood from multiple points in the patient, namely the superior vena cava, right atrium, and the right ventricle, while returning blood to the patient's pulmonary artery. Further, the catheter of the present invention is less likely to be moved or dislodged than catheters currently available in the art, thus making the catheter particularly useful for portable lung assist devices. The present invention also relates to methods for inserting the catheter into the patient and using the catheter with a lung assist device. The present invention also relates to a portable lung assist device. In one embodiment, the portable lung assist device includes an integrated oxygenator, blood pump, and catheter. In one embodiment, the portable lung assist device of the present invention does not require an oxygen tank, but instead can provide oxygen to a subject's blood from ambient air.

Description

CATHETER FOR PORTABLE LUNG ASSIST DEVICE

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Patent Application Serial Nos.

61/983,804, filed April 24, 2014; 62/050,507, filed September 15, 2014; and 62/092,387, filed December 16, 2014, which are each incorporated herein by reference in their entirety.

BACKGROUND OF THE INVENTION

Lung diseases are the third largest cause of mortality in the U.S., with more than 350,000 deaths annually attributed to lung disease. A wide range of disease processes culminate in end-stage lung disease, including adult respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), interstitial lung diseases, and cystic fibrosis. Patients with lung failure are usually treated with mechanical ventilation and sedation, with the hope that their native lung condition improves with therapy. In some patients that fail mechanical ventilation, extra-corporeal membrane oxygenation (ECMO) is used to support the patients' lungs as a bridge to recovery or lung transplantation.

The currently available technology for ECMO generally requires large beside machines, e.g., a machine that includes a pump, an oxygenator, an air filter, a gas blender, a heat exchanger, and an oxygen tank. The large, heavy nature of these machines can prevent a patient from being able to leave their bed during treatment. Further, most patients on ECMO have to be anesthetized and sedated, leading to deconditioning of these patients.

Some ambulatory ECMO devices for patients with lung failure have been used successfully. However, the ambulatory ECMO devices currently available are still relatively large, heavy, and cumbersome. These devices incorporate the same components from a standard ECMO machine, or marginally smaller versions of these same components, into a system that is placed on a cart or other means for moving the system so that the patient can get out of bed and move around. Therefore, such ambulatory ECMO devices are not truly portable devices that can allow a patient to move around on his or her own, but instead are systems that can allow the patient to change their location, but only with the help of another person that can push the heavy cart that holds the system. Further, these ambulatory ECMO systems require compressed oxygen tanks that must be changed regularly in order to provide a continuous source of oxygen to the system.

In addition, currently available ECMO systems require the presence of trained, licensed perfusion specialists to be physically available around the clock to ensure that these systems are functioning properly. The need for near constant supervision by a specialist greatly reduces the freedom of patients using such systems.

ECMO systems and other lung assist devices also require the use of a catheter for transferring blood from the patient, through an extra-corporeal oxygenator, and back into the patient. However, there are a number of issues associated with currently available catheters that are used in ECMO. For example, when using the AVALON ELITE dual lumen catheter (Maquet Holdings), there can be a significant amount of oxygenated blood that gets recirculated through the catheter and back to the lung assist device instead of circulating through the patient. This recirculation of oxygenated blood reduces the performance and efficiency of the lung assist device. In addition, the performance of currently available catheters is dependent on maintaining a constant position of the catheter in the patient. However, if the patient moves his or her neck, which is generally the entry point of the catheter, the catheter can shift or dislodge, thereby causing poor performance of the lung assist device, and requiring the catheter to be repositioned so that the lung assist device can work optimally. Further, the potential for currently available catheters to be easily moved or dislodged makes them undesirable for use with a portable lung assist device, because a patient using an ambulatory lung assist device is more likely to cause the catheter to shift position.

Some examples of dual lumen catheters described in the art as being useful for ECMO include a first lumen for draining un-oxygenated blood from the right atrium or superior vena cava, while a second lumen is used to send oxygenated blood into the pulmonary artery. For example, Shorey et al. (U.S. Patent App. Pub. No. 2009/0005725) and Kelly et al. (U.S. Patent App. Pub. No. 20013/0158338) both describe a coaxial dual lumen catheter having an outer lumen with apertures suitable for draining un-oxygenated blood from the right atrium and/or superior vena cava, while the inner lumen extends through the tricuspid valve and right ventricle so that the tip of the inner lumen can be positioned within the pulmonary artery. The outer lumen of the catheter described in Shorey and Kelly does not extend the full length of the catheter, so that the apertures used to drain un-oxygenated blood into the outer lumen are sufficiently separated from the aperture(s) at the tip of the inner lumen so as to minimize or prevent recirculation. However, Shorey and Kelly do not describe a catheter capable of draining un- oxygenated blood from the right ventricle in addition to the right atrium and/or superior vena cava. Accordingly, there is no catheter described in the art having the required construction and design to effectively drain blood from both the right atrium and right ventricle, but a catheter with such a unique construction and design would greatly improve the efficiency of an ECMO device.

Thus, there is a continuing need in the art for a catheter for lung assist devices that minimizes the recirculation of oxygenated blood, and that prevents or minimizes the need for re- positioning the catheter, or the risk of the catheter dislodging, due to patient movement, that is suitable for draining blood from both the right atrium and right ventricle. There is also a need in the art for a portable integrated lung assist device that can allow a patient to move around without the help of another person and that does not need require constant supervision by a specialist. Further, there is a need for such a device that does not require an oxygen tank for the oxygen source. The present invention addresses these continuing needs in the art.

SUMMARY OF THE INVENTION

The present invention relates to a catheter for use with a lung assist device that minimizes or eliminates the recirculation of oxygenated blood. In addition, the catheter of the present invention can be used to drain blood from multiple points in the patient, namely the superior vena cava (SVC), right atrium, and the right ventricle.

In one embodiment, the catheter of the present invention comprises: a first tube having a lumen with at least one opening to the lumen suitable for draining substantially un- oxygenated blood from a patient and transferring the drained blood to the lung assist device; and a second tube having a lumen with at least one opening to the lumen suitable for returning oxygenated blood to the patient; wherein at least one of the openings of the first tube is positioned along the length of the first tube such that the opening is positioned in the patient's right ventricle when inserted into a patient, and wherein at least one of the openings of the second tube is positioned along the length of the second tube such that the opening is positioned in the patient's pulmonary artery when inserted into the patient. In one embodiment, at least one of the openings of the first tube is positioned along the length of the first tube such that the opening is positioned in the patient's superior vena cava when inserted into the patient. In another embodiment, at least one of the openings of the first tube is positioned along the length of the first tube such that the opening is positioned in the patient's right atrium when inserted into the patient. In one embodiment, the catheter is sized for blood flow in the range of about 3 to 4 L per minute. In one embodiment, at least a portion of the first tube is reinforced with wire. In one embodiment, at least a portion of the second tube is reinforced with wire.

The present invention also relates to methods for using the catheter, In one embodiment, the method is a method for oxygenating blood in a subject, comprising: inserting a catheter into a subject, such that the catheter enters the subject's heart via the superior vena cava, passes through the right atrium and right ventricle, and extends into the pulmonary artery, wherein the catheter comprises a first tube and a second tube; draining blood from the subject's right ventricle via the first tube; oxygenating the drained blood; returning the oxygenated blood to the subject's pulmonary artery via the second tube. In one embodiment, the first and second tubes run substantially parallel to each other along at least a portion of the length of the catheter. In another embodiment, the first tube and second tube are coaxial along at least a portion of the length of the catheter. In one embodiment, blood is also drained from the subject's superior vena cava via the first tube. In one embodiment, blood is also drained from the subject's right atrium via the first tube. In one embodiment, blood is oxygenated using an extra-corporeal membrane oxygenation (ECMO) device. In one embodiment, the catheter is inserted into the subject using guiding mechanism, for example a guide wire or an X-ray guidance system.

The present invention also relates to a portable lung assist device, comprising: an oxygenator, having a first chamber and a second chamber, the first chamber having an inlet and an outlet, the second chamber having an inlet and an outlet, and a membrane separating the first chamber and the second chamber; a means for supplying a sweep gas to the inlet of the first chamber of the oxygenator; a catheter, having a first lumen and a second lumen; and a pump; wherein the first lumen is connected to the pump, the pump is connected to the inlet of the second chamber of the oxygenator via a third lumen, and the second lumen is connected to the outlet of the second chamber of the oxygenator; wherein when the first lumen and second lumen are also connected to a blood vessel of a subject, blood can flow from the subject through the first lumen, through the pump, through the third lumen, through the second chamber of the oxygenator, and through the second lumen back into the subject; and wherein the subject's blood can be oxygenated via transfer of oxygen across the membrane in the oxygenator. In one embodiment, the sweep gas is air. In one embodiment, at least a portion of the catheter is surgically implantable. In one embodiment, the means for supplying a sweep gas to the oxygenator is a fan. In one embodiment, the pump is a centrifugal pump or an axial pump. In one embodiment, the device further comprises an air filter for filtering the sweep gas. In one embodiment, the device further comprises a power source. In one embodiment, the device further comprises a flow sensor for measuring the rate of blood flow through the device. In one embodiment, the device further comprises at least one sensor for measuring the oxygenation level of blood in the device. In one embodiment, the at least one lumen of the catheter is inserted into the subject's pulmonary artery.

BRIEF DESCRIPTION OF THE DRAWINGS

The following detailed description of preferred embodiments of the invention will be better understood when read in conjunction with the appended drawings. For the purpose of illustrating the invention, there are shown in the drawings embodiments which are presently preferred. It should be understood, however, that the invention is not limited to the precise arrangements and instrumentalities of the embodiments shown in the drawings.

Figure 1, comprising Figures 1A-1C, is a set of illustrations showing a prior art catheter.

Figure 2 is a diagram of an exemplary embodiment of a catheter positioned within a subject's heart.

Figure 3 is an illustration showing two exemplary embodiments of the device of the present invention. Figure 3 A depicts an exemplary dual-lumen catheter with parallel tubes (not-to-scale). Figure 3B depicts an exemplary dual-lumen catheter with coaxial tubes (not-to- scale).

Figure 4, comprising Figures 4A through 4F, is a set of diagrams of an exemplary embodiment of a coaxial catheter of the present invention, including non-limiting examples of the dimensions of various portions of the catheter and the size and location of openings.

Figure 5 is a diagram of an exemplary embodiment a catheter positioned within a subject's heart and connected to an exemplary embodiment of a portable lung assist device. Figure 6 is a flow diagram of one embodiment of the method of the present invention.

DETAILED DESCRIPTION

It is to be understood that the figures and descriptions of the present invention have been simplified to illustrate elements that are relevant for a clear understanding of the present invention, while eliminating, for the purpose of clarity, many other elements found in the field of artificial lungs or lung assist devices, and catheters for use with lung assist devices. Those of ordinary skill in the art may recognize that other elements and/or steps are desirable and/or required in implementing the present invention. However, because such elements and steps are well known in the art, and because they do not facilitate a better understanding of the present invention, a discussion of such elements and steps is not provided herein. The disclosure herein is directed to all such variations and modifications to such elements and methods known to those skilled in the art.

Definitions

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although any methods and materials similar or equivalent to those described herein can be used in the practice for testing of the present invention, the preferred materials and methods are described herein. In describing and claiming the present invention, the following terminology will be used.

It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

The articles "a" and "an" are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, "an element" means one element or more than one element.

"About" as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20%, ±10%, ±5%, ±1%, or ±0.1% from the specified value, as such variations are appropriate. The terms "patient," "subject," "individual," and the like are used interchangeably herein, and refer to any animal amenable to the systems, devices, and methods described herein. Preferably, the patient, subject or individual is a mammal, and more preferably, a human.

Ranges: throughout this disclosure, various aspects of the invention can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range.

Catheters For Use With Lung Assist Devices

The present invention relates in part to catheters for use with a lung assist device, and a method for using such catheters, that minimize or eliminate the recirculation of oxygenated blood. In addition, the catheters described herein can be used to drain blood from multiple points in the patient, namely the superior vena cava (SVC), right atrium, and the right ventricle. Further, these catheters are less likely to be moved or dislodged than catheters currently available in the art. These catheters are particularly useful in conjunction with an ECMO device or other lung assist devices, especially portable versions of such devices, and can significantly improve the efficiency of such devices.

In one embodiment, the catheter is a dual lumen catheter, wherein a first lumen includes at least one opening that is used for draining blood from the superior vena cava, right atrium, and/or right ventricle. The drained blood can be sent to an ECMO device or other type of lung assist device for oxygenation. After the blood is circulated through the ECMO device and sufficiently oxygenated, the oxygenated blood is returned to the patient via the second lumen having at least one opening that is preferably positioned within the pulmonary artery.

The most commonly used catheter in veno-venous ECMO devices is a dual lumen catheter that is configured to be placed in the right internal jugular vein. Referring now to Figure 1 , a currently known catheter is shown for purposes of comparison to the device of the present invention. This prior art catheter 2 comprises a single tube 3 having two lumens that can be inserted into the patient. Catheter 2 allows removal of venous (un-oxygenated) blood from the inferior vena cava (IVC) and superior vena cava via one lumen so that it can be sent to a lung assist device for oxygenation. Oxygenated blood is then returned to the patient via a second lumen into the right atrium, directed against the tricuspid valve, with the hope that the oxygenated blood will flow past the tricuspid valve and into the pulmonary circulation (see Figure IB). However, use of this catheter design is often associated with the recirculation of oxygenated blood within the patient, which reduces the efficiency of the lung assist device. Specifically, there is a significant amount of oxygenated blood that gets re-circulated, as some oxygenated blood will mix with the SVC and IVC blood and will return to the lung assist device for oxygenation, rather than flowing through the tricuspid valve. This re-circulation fraction is variable, depending on the position of the catheter, rotation of the catheter, and the patient volume status. Further, since the performance of this type of catheter is very much dependent on its position, any patient movement, e.g., flexion and extension of the neck, will move the catheter and result in changes in the position of the outflow hole against the tricuspid valve. It is not unusual that repeated trans-esophageal studies on the same patient will be required to re-position the catheter, as the patient awakens and invariably moves his or her neck. Accordingly, the efficiency of this catheter is very much dependent on its position, which can change

significantly.

Conversely, the catheters of the present invention minimize or prevent recirculation of oxygenated blood by providing adequate spacing between the inflow and outflow openings, and by segregating the inflow and outflow openings within different areas of the patient's circulatory system. Specifically, the catheters of the present invention have one or more outflow openings located in the pulmonary artery, while the inflow openings are located within the right atrium, right ventricle, and/or superior vena cava. Thus, the outflow openings are separated by the inflow openings located in the right ventricle via the pulmonary valve in the pulmonary artery. The inflow openings located in the right atrium and superior vena cava are further separated from the outflow openings by the tricuspid valve. On the other hand, the outflow openings in prior art catheter 2 are not sufficiently segregated from the inflow openings to prevent significant recirculation of oxygenated blood. Further, prior art catheter 2 is not sufficiently stabilized in comparison to the catheters of the present invention because no parts of catheter 2 are positioned through either the tricuspid or pulmonary valves.

Referring now to Figure 1C, another prior art catheter is shown for purposes of comparison to the devices of the present invention. Catheter 4 is a dual lumen catheter wherein the two lumens are coaxial. The tube 5 containing the outer lumen does not extend the full length of the catheter, but instead the outer wall of tube 5 is fused to the wall of the inner lumen at a point 6 within the right atrium. The tube 7 containing the inner lumen then is fed through the tricuspid valve and right ventricle and into the pulmonary artery, wherein oxygenated blood can be returned to the patient via openings 8. Tube 5, containing the outer lumen, has a number of openings 9 for draining un-oxygenated blood from the SVC and right atrium. However, tube 5 is not capable of draining blood from the right ventricle because tube 5 does not have any openings positioned within the right ventricle that are in communication with the outer lumen.

Accordingly, catheter 4 cannot drain blood from the right ventricle. Therefore, the catheters of the present invention have a significant advantage over catheter 4 because it can greatly improve the efficiency of a lung assist device by draining blood from the right ventricle in addition to the right atrium and SVC.

Referring now to Figure 2, an exemplary embodiment of a catheter 10 of the present invention is shown. Catheter 10 comprises a first tube 20, having a lumen for directing the inflow of blood from the patient to a lung assist device 40, and a second tube 30, having a lumen for directing the outflow of blood from lung assist device 40 back into the patient. As shown in Figure 2, first tube 20 can be positioned so that it extends through the tricuspid valve and into the right ventricle. First tube 20 comprises one or more openings 22 in the wall of the tube for draining blood from the superior vena cava, right atrium, and/or right ventricle into the lumen of first tube 20. First tube 20 also comprises an opening 24 at or near its distal tip, which can be used to drain blood specifically from the right ventricle. Second tube 30 of catheter 10 is positioned so that it extends through the tricuspid valve and right ventricle, and through the pulmonary valve into the pulmonary artery, so that an opening 32 at or near the tip of second tube 30 can be used to send oxygenated blood directly into the pulmonary artery. In one embodiment, second tube 30 can also include one or more openings in the wall of the tube, particularly near the tip of the tube, instead of or in addition to opening 32. Referring now to Figure 3 A, an embodiment of catheter 10 similar to that as shown in Figure 3 is depicted in a straight- line diagram. Catheter 10 may generally include parallel tubes 20 and 30. Tube 20 includes openings 22 and 24 suitable for being positioned within a patient's superior vena cava, right atrium, and right ventricle for draining blood from the patient. Tube 30 includes an opening 32 suitable for returning blood to the patient after oxygenation. Tube 30 is generally longer than tube 20 so that a portion of the distal end can be positioned within the pulmonary artery.

In another embodiment and as shown in Figure 3B, catheter 12 may include tubes 20 and 30 that can be configured coaxially. In such an embodiment, tube 30 is the inner tube of the coaxial arrangement, wherein tube 30 extends beyond a point 72 where outer tube 20 fuses with at least a portion of the wall of tube 30. Accordingly, catheter 12 can be bent or flexed at a point 70, such that openings 22 are positioned within the patient's superior vena cava and/or right atrium, while at least one of openings 24 are positioned within the patient's right ventricle. Opening 32 at or near the distal end of catheter 12 can then be positioned within the patient's pulmonary artery.

It should be appreciated that the catheters of the present invention are not limited to any particular dimensions of length, gauge or other sizing characteristic. Accordingly, the catheters of the present invention can be any size, depending on the size or dimensions of the patient's body. As would be understood by a person skilled in the art, the length of the catheters and the location of the various openings must be designed such that un-oxygenated blood can be suitably drained via the superior vena cava, right atrium, and/or right ventricle, while oxygenated blood can be returned at least to the patient's pulmonary artery. For example, another embodiment of a coaxial catheter of the present invention is shown in Figures 4A-4E, including specific dimensions and location of openings. In certain embodiments, the diameter of the lumens in the catheter of the present invention will be sized to allow flow of about 3 to 4 L per minute of blood. Similarly, the size and location of the openings in the catheter tubes may be sized to maintain such a flow rate. In one embodiment, the openings may be sized as large as possible without compromising the integrity of the catheter. However, the catheter can be sized to allow for more or less blood flow than 3 to 4 L per minute depending on a number of factors, including, but not limited to, the efficiency of the connected lung assist device or the need of blood oxygenation assistance of the patient For example, in some embodiments, the catheter can be sized to allow for blood flow rates of 5, 6, 7, or 8 L per minute or more, or 0.5, 1, 1.5, or 2 L per minute or less.

The catheter of the present invention may be constructed from any materials currently known in the art used in the construction of catheters, and particularly catheters associated with lung assist devices for insertion into a patient's vasculature. In one embodiment, at least a portion of one or both tubes of the dual lumen catheter of the present invention are reinforced with wire. The wire reinforcement can be designed accordingly so that catheter can be suitably advanced into position within the patient, and so that the catheter is stabilized in the optimal location, once positioned. Accordingly, the catheter of the present invention may include portions or regions having the desired stiffness, rigidity or flexibility necessary for proper insertion into the subject and subsequent functionality. Accordingly, catheter 10 can be positioned within the patient so that the inflow openings 22 and 24 in first tube 20 can be positioned at several sites within the patient, such as the right ventricle, the right atrium, and superior vena cava, while the one or more outflow openings 32 located at the distal tip of second tube 30 can be positioned to deliver the oxygenated blood into the main pulmonary artery. The multitude of inflow openings 22 and 24 significantly improve the flow dynamics of the blood that is being drained from the patient. Further, the distance between the inflow and outflow openings 22 and 24 provides the significant and unexpected result of minimal or no recirculation of oxygenated blood. The positioning of catheter 10 in the patient, such that the patient's pulmonary valve is between the inflow and outflow openings, also aids in preventing the re-circulation of oxygenated blood.

In addition, the configuration of the catheters of the present invention permit the catheters to be held in a more stable position than other catheters known in the art. The increased stability is due at least in part to both first tube 20 and second tube 30 being inserted through the tricuspid valve and into the right ventricle. The second tube 30 of catheter 10 is significantly longer than first tube 20, and this longer portion of second tube 30 can be guided through the pulmonary valve and into the main pulmonary artery via methods commonly used in the art, for example a guide wire or via X-ray guidance. This extended portion of second tube 30 also provides increased stability to the catheter by using the pulmonary valve as an additional stabilization point. In one embodiment, at least a portion of first tube 20 is fused or connected to second tube 30. In one embodiment, the entire length of first tube 20 that is to be positioned within the patient is connected to second tube 30, which provides stability to the positioning of both tubes.

Although the positioning of a portion of the catheter within the pulmonary artery is the primary reason for the high stability of the catheter within the patient, there are additional features which provide optimal stability of the catheter of the present invention. In one aspect, migration of the inserted catheter is reduced due to the use of draining points within the right ventricle. By draining blood from the right ventricle and therefore decreasing the right ventricle blood volume, the right ventricle systolic force is reduced, thereby minimizing catheter migration. In another aspect, the degree of wire reinforcement of first tube 20 and second tube 30 can be modified to provide optimal stability of the catheter once positioned within the patient.

Systems and Methods for Extracorporeal Membrane Oxygenation

The present invention also relates to systems for extracorporeal membrane oxygenation (ECMO) and their methods of use. For example, the present invention relates to a portable, integrated system that supports failing human lungs, while allowing a patient to optionally move without the required assistance of another person. Accordingly, the present invention addresses the need for a compact system that can be used to oxygenate a patient's blood or to remove carbon dioxide while the patient is waiting for recovery of his or her own lungs, or as a bridge to lung transplantation. In one embodiment, the systems may assist a patient's lungs for 30 days or more. In one embodiment, the systems and methods relate to veno- venous ECMO. In one embodiment, the systems and methods relate to arterio-venous ECMO.

In one embodiment, the systems may include a pump, an oxygenator, a means for supplying air or oxygen to the oxygenator, and a surgically implantable catheter for the removal and return of blood from the patient. In one embodiment, the system optionally includes a heat exchanger. In another embodiment, the system may include at least one sensor, for example a flow sensor or an oxygen sensor. In yet another embodiment, the system may include an oxygen source, preferably a low-weight, portable oxygen source.

Referring to Figure 5, the system 50 may include a lung assist device 40 and a catheter 10. Catheter 10 of system 50 may be any embodiment of the catheters forming part of the present invention, as described herein. Lung assist device 40 serves to provide lung support to a subject as follows. Blood is drawn from a subject through catheter 10, having a first lumen and a second lumen, with the assistance of a pump 14. Pump 14 of lung assist device 40 pushes the blood through a cannula, conduit or a piece of tubing 15, into an oxygenator 16 of lung assist device 40, wherein oxygen is transferred into the blood and/or carbon dioxide is removed from the blood. The oxygenated blood is then returned back into the subject via the second lumen in catheter 10. In certain embodiments, lung assist device 40 is compact and portable, such that all components of the device other than catheter 10 can be completely contained within a portable container or housing, for example a container suitable for carrying by the subject, or a container that can be placed on wheels or a cart for easy portability by the subject.

In certain embodiments, the circuit formed by the catheter 10, pump 14, and oxygenator 16 has a relatively small volume, and the blood traveling through the circuit is outside of the subject for only a relatively short amount of time, thereby eliminating the requirement for a heat exchanger or other component to maintain the temperature of the blood within a range acceptable for medical use. The lack of a need for a heat exchanger enables the lung assist device component 40 of system 50 of the present invention to be smaller and, therefore, more portable than ECMO devices currently available. However, in one embodiment, system 50 may optionally include a heat exchanger to ensure that the subject's blood is maintained within an acceptable temperature range. It should also be appreciated that lung assist device 40 may include any other component or feature found in standard lung assist devices, and is not limited to any particular equipment or component design.

Further, the oxygenator of the device 40 may include a fan component that pushes air through the oxygenator in order to oxygenate the subject's blood. Accordingly, device 40 of does not require a separate oxygen source to provide oxygen to the subject's blood, but instead may optionally use ambient air in the environment surrounding device 40. The lack of a need for an oxygen source also enables the lung assist device 40 to be smaller and, therefore, more portable than ECMO devices currently available. However, device 40 or system 50 generally, may include a separate oxygen source, such as an oxygen tank, to provide increased oxygen concentration to the oxygenator in cases where a higher oxygen concentration than that available in the ambient air is desired.

As mentioned previously, system 50 also includes catheter 10 that is used to remove blood from the patient in order to circulate the blood through an extracorporeal circuit for oxygenation, before returning the blood to the patient. In one embodiment, a portion of catheter 10 is surgically implanted in the patient. In one embodiment, catheter 10 is a dual lumen catheter wherein a first lumen is used for removing blood from the subject and a second lumen is used for returning oxygenated blood to the subject. In other embodiments, standard catheters or cannulas may be used in conjunction with lung assist device 40, using standard insertion and placement techniques suitable for the catheter or cannula elected. An exemplary cannula known in the art that can be used for the device of the present invention is the Avalon ELITE bi-caval dual lumen catheter. Other exemplary cannulae useful in the device of the present invention are described by Shorey (US. Pat. App. No. 12/145738); Richardson et al. (U.S. Pat. No. 8,118,723); and Reichenbach et al. (U.S. Pat. No. 8,231,519 and US. Pat. App. No. 13/561,197), all of which are incorporated herein by reference in their entirety.

In one embodiment, the means for withdrawing and returning blood is a single- site veno venous cannulation, wherein a dual-lumen cannula is inserted into the subject. In one embodiment, the cannula is catheter 10 as previously described herein. In one embodiment, the dual-lumen cannula is inserted into the jugular vein, extending through the right atrium and into the inferior vena cava. In such an embodiment, venous blood can be withdrawn from the vena cava via at least one port in a first lumen of the catheter, while oxygenated blood can be returned to the patient's right atrium via at least one port in a second lumen. In another embodiment, a dual-lumen cannula can be inserted into the subject's pulmonary artery. In such an embodiment, oxygenated blood is returned to the subject's pulmonary artery. In various embodiments, the ports in the first lumen and second lumen of the dual-lumen cannula are positioned to reduce circulation of blood directly between the two lumen.

Alternatively, means for withdrawing and returning blood can be a two-site venovenous cannulation. In one embodiment, a first cannula is inserted in the jugular vein, extending into the right atrium, while a second cannula is inserted into the femoral vein, extending into the inferior vena cava. In such an embodiment, blood is withdrawn via the femoral cannula into the device, then oxygenated blood is reinfused into the patient via the jugular cannula.

In another embodiment, the means for withdrawing and returning blood is a single-site or two-site arterio-venous cannulation. In such an embodiment, the first cannula or lumen, used for returning oxygenated blood to the subject, is inserted into the subject's pulmonary artery. In one embodiment, the second cannula or lumen, used for withdrawing blood from the subject for oxygenation, can be inserted into any blood vessel as would be understood by a person skilled in the art.

In one embodiment, system 50 and/or lung assist device 40 may include at least one quick-connect mechanism for removably connecting respective components together. In one embodiment, a surgically implanted cannula may comprise a quick-connect port outside the subject's body for connecting the blood pump or other component to the cannula. In such an embodiment, the surgically implanted cannula can be disconnected from the other components of the device and/or system, for example, when one or more components need to be replaced or when oxygenation of the subject's blood is not required. Such a quick-connect mechanism would be suitable for medical applications, and would allow the cannula or catheter 10 to be kept in place in the subject for later use, thereby eliminating the need to remove a surgically implanted portion of the device or system. In one embodiment, the quick-connect mechanism further comprises a seal mechanism for isolating the internal lumen of the cannula or catheter 10 from the outside environment, thereby eliminating the risk of blood loss and reducing the risk of infection in the subject. An example of a quick-connect mechanism suitable for use in the present invention is described by Dormanen et al. (PCT/US2013/025703)

As mentioned previously, device 40 includes a pump 14 that is used to maintain the desired flow rate of blood through device 40 of system 50. In various embodiments, the pump can supply enough head pressure to overcome the resistance of an oxygenator and any tubing or cannulae used to direct the flow of blood in the system. In various embodiments, the pump is any type of pump suitable for use with human blood, as understood by a person skilled in the art. In one embodiment, the pump is a centrifugal pump. In another embodiment, the pump is a pneumatic pump. In yet another embodiment, the pump is an axial or impeller pump.

The pump component can be used to provide a flow rate of blood through device 40 and system 50 that is typically in the range of 1 to 5 liters per minute (L/min). In a preferred embodiment, the maximum flow capacity of the pump is about 2.5 L/min. In various

embodiments, the pump generates enough pressure to circulate blood through the system without causing significant hemolysis. In one embodiment, the pressure change (ΔΡ) across the pump is at least 40 mm Hg in order to achieve the desired flow rate of blood through the system. In another embodiment, the ΔΡ is about 50 mm Hg. However, the pump used is not limited to the values for flow rate and/or ΔΡ described herein, and can be any value as would be understood by a person skilled in the art.

Pumps that can be used in the lung assist device 40 of system 50 may be standard in the art. Such pumps can be those sold separately commercially, or can be incorporated into a device having other components, such as a Left Ventricular Assist Device (LVAD). Exemplary pumps that can be used in the present invention can be found in the Thoratec HEARTMATE II LVAD, Thoratec Paracorporeal Ventricular Assist Device (PVAD), or Thoratec Implantable Ventricular Assist Device (IV AD). Other exemplary blood pumps are described in McBride et al. (U.S. Pat. No. 7,841,976); Tansley et al. (U.S. Pat. No. 8,366,599); and Campbell et al. (U.S. Pat. No. 8,535,211), all of which are incorporated herein by reference in their entirety.

Also mentioned previously, device 40 of system 50 includes an oxygenator for transferring oxygen from an oxygen source to the subject's blood. In one embodiment, the oxygenator comprises a membrane that allows oxygen to diffuse into the blood while also allowing carbon dioxide to diffuse out of the blood. In such an embodiment, the oxygenator comprises two chambers separated by a semipermeable membrane. A pump delivers venous blood, or blood in need of oxygenation or carbon dioxide removal from another location in the subject, from the subject to the oxygenator, wherein the venous blood flows through the first chamber of the oxygenator. A sweep gas is simultaneously delivered to the second chamber of the oxygenator. As the blood flows through the first chamber, gas exchange occurs across the membrane separating the first and second chambers. In such a gas exchange, oxygen is transferred from the sweep gas in the second chamber into the blood in the first chamber.

Further, carbon dioxide present in the blood will be transferred out of the blood into the sweep gas in the second chamber. The blood that exits the second chamber is returned to the patient, while the gas that exits the first chamber can be sent to the ambient environment, or to an exhaust vent in the room. In one embodiment, the oxygenator has a minimum surface area that corresponds to the delivery of oxygen to the patient's blood at a rate of about 180 cc/min.

In one embodiment, the sweep gas comprises fresh air that is delivered to the second chamber via a fan. In another embodiment, the sweep gas comprises a mixture of air and oxygen that is blended prior to being delivered to the second chamber. In such an embodiment, a feed gas, such as pure oxygen, can be combined with ambient air to form the sweep gas. Further, in such an embodiment, device 40 may comprise additional components, such as an air blender or mixer, and a sweep gas pump to pump the mixed sweep gas to and through the second chamber of the oxygenator.

The concentration of carbon dioxide and oxygen in the blood exiting the oxygenator, i.e., the blood that will be returned to the patient, is primarily determined by the partial pressures of the respective gases in the blood and the sweep gas, and the characteristics of both the membrane and the first and second chambers. For example, if the surface area of the membrane is relatively large compared to the volume of the first chamber, a relatively high rate of gas diffusion across the membrane can occur. Additionally, if the difference in partial pressure of a gas species across the membrane, i.e., the difference in partial pressure between the first and second chambers, is significantly high, then a relatively high rate of gas diffusion can occur.

Other variables that can affect the oxygen uptake and carbon dioxide elimination in the blood in the second chamber are the flow rate of sweep gas through the first chamber, the flow rate of blood through the second chamber, and the absolute pressure inside the first chamber. In one embodiment, the sweep gas can flow in a direction countercurrent to the flow of blood. In another embodiment, the sweep gas can flow concurrently to the flow of blood.

In various embodiments, the oxygenator of device 40 can be a standard oxygenator known in the art. Exemplary oxygenators include the Medtronic AFFINITY

FUSION oxygenation system, Medtronic AFFINITY NT oxygenation system, Medtronic AFFINITY PIXIE oxygenation system, Medtronic MINIMAX PLUS oxygenation system, Maquet QUADROX oxygenation system, Sorin KiDS oxygenator, Sorin APEX oxygenator, Sorin BMR oxygenator, Sorin PRIM02X oxygenator, Sorin SYNERGY oxygenator, or Sorin SYNTHESIS oxygenator. In one embodiment, the oxygenator can be a membrane ventilator. Exemplary membrane ventilators include the Novalung MINILUNG membrane ventilator, the Novalung iLA membrane ventilator, and the Novalung XLUNG membrane ventilator. In one embodiment, the pump and oxygenator of device 40 can be an integrated unit, such as the blood- pump oxygenator described by Gellman et al. (U.S. Pat. No. 8,496,874), incorporated by reference herein in its entirety.

In various embodiments, operating parameters in the lung assist device and system generally, such as the sweep gas flow rate, blood flow rate, and gas pressure in the oxygenator, can be controlled to achieve the desired performance. In one embodiment, the sweep gas flow rate can be up to about 15 L/min. In one embodiment, the gas pressure can be up to about 30 mm Hg. In one embodiment, the blood flow rate can be up to about 5 L/min. However, the operating parameters of the system are not limited to the values listed herein. Generally, a relatively low blood flow rate through the oxygenator requires a correspondingly high gas flow rate and/or gas pressure to achieve sufficient blood oxygenation. Conversely, a relatively high blood flow rate can reduce the gas flow rate and/or gas pressure values required for sufficient blood oxygenation.

Additionally, the operating parameters of the lung assist device and system generally can be adjusted depending on whether the system is primarily being used to remove carbon dioxide from the blood instead of oxygenation. For example, a relatively low flow rate of blood through device 40 is needed when carbon dioxide removal, rather than oxygen delivery, is the primary focus of system 50 functionality.

In one embodiment, ambient air, i.e., air in the environment immediately surrounding device 40, is used as the sweep gas feed to the oxygenator. Ambient air typically comprises 20.95 % oxygen and less than 0.04% carbon dioxide by volume. By using ambient air as the gas feed for the oxygenator, the system eliminates the need for an oxygen tank or other source of oxygen, thereby increasing portability of the system. Alternatively, in another embodiment, ambient air can be mixed with oxygen from an oxygen source prior to be supplied to the oxygenator in order to increase the concentration of oxygen in the gas feed, thereby increasing the rate of oxygen transfer to the blood.

Accordingly, the devices and systems of the present invention may include a concentrated oxygen source to supply oxygen to the subject's blood via the oxygenator. In one embodiment, the concentrated oxygen source is an oxygen canister tank, whereby compressed oxygen in the form of a liquid or gas is stored and supplied to the system as needed through a valve. In such embodiment, oxygen from the concentrated oxygen source may be added to ambient air in order to increase the concentration of oxygen in the sweep gas being supplied to the oxygenator.

The devices and systems of the present invention may further comprise a power source, or a means for supplying power. In one embodiment, the power source can be a battery, preferably a compact battery pack that is suitable for a portable device and system. In one embodiment, the battery comprises a lithium battery. In another embodiment, the power source can be provided via a power cord suitable for connecting the system components to an electrical outlet, in cases where the patient is waiting for the battery to be recharged, or when the patient desires to remain in a location that is suitably close to an electrical outlet.

In various embodiments, the devices and systems may include additional components that improve the performance of blood oxygenation and lung assistance. Such components may include, but are not limited to: a heat exchanger, at least one sensor, an air filter, and a control panel or other means for controlling the system components.

For example, in one embodiment, the system includes a heat exchanger. In such an embodiment, the heat exchanger is used to maintain the temperature of the subject's blood at or close to the subject's natural body temperature in order to prevent or reduce the potential for causing adverse health effects associated with a decrease in temperature of the blood while the blood is outside the subject's body. In one embodiment, the heat exchanger is small and compact in size in order to maintain portability of the overall system while serving to minimize the effects of the patient's blood being exposed to ambient, i.e., room temperature. In one embodiment, the heat exchanger is a shell and tube heat exchanger.

In another example, the system includes at least one sensor for measuring variables related to the operation of the system. In one embodiment, the system includes an oxygen sensor for determining the level of oxygen in the subject's blood. In another

embodiment, the system includes a carbon dioxide sensor for determining the level of carbon dioxide in the subject's blood. In one embodiment, the oxygen and/or carbon dioxide sensors can be used for measuring the concentration of a gas in the blood entering the lung assist device, i.e., pre-oxygenation. In another embodiment, the oxygen and/or carbon dioxide sensors can be used for measuring the concentration of a gas in the blood returning to the patient, i.e., post- oxygenation. In one embodiment, the system includes at least one sensor for determining the composition of oxygen and/or carbon dioxide in the sweep gas. In one embodiment, the system includes at least one flow sensor for measuring the flow rate of blood at a desired location in the system. In one embodiment, the system includes a flow sensor for measuring the flow rate of sweep gas in the oxygenator. In one embodiment, the system includes temperature sensors for determining the temperature of the blood at a desired location in the system, for example, the temperature of blood in the second lumen as it is being returned to the patient. In one embodiment, the system includes an air filter for filtering particulates or other impurities from the gas being supplied to the oxygenator. In one embodiment, the filter is capable of filtering about 95% of particles that are 0.3 microns or larger.

In various embodiments, the system includes means for controlling the lung assist device, for example, to control variables such as, but not limited to, the flow rate of blood through the device, the flow rate of air through the device, the composition of sweep gas, and the temperature of blood flowing through the system. In one embodiment, the control means is a compact controller integrated with system, comprising a touch screen or other means for entering and/or displaying data. In another embodiment, the control means may comprise a computer processor integrated with the system that can be controlled via a wireless connection to a computer that is not physically connected to the system.

In one embodiment, integrated software may be used to automatically adjust the flow, pressure, the sweep gas flow, and/or other parameters to optimize and/or meet the patient's physiologic needs. In one embodiment, a wireless remote monitoring system can be included in device of the present invention to allow the subject or a caretaker to monitor the subject and/or the ECMO circuit performance.

The present invention also relates to methods for oxygenating blood in a subject. As contemplated herein, the methods generally include the steps of inserting a catheter comprising a first tube and a second tube into a subject, such that the catheter enters the subject's heart via superior vena cava, passes through the right atrium and right ventricle, and extends into the pulmonary artery, draining blood from the subject's right ventricle via the first tube, oxygenating the drained blood, and returning the oxygenated blood to the subject's pulmonary artery via the second tube. For example, referring to Figure 6, in one embodiment, the method 100 of the present invention comprises the steps of: (110) providing a dual-lumen catheter comprising two tubes, wherein the first tube comprises a lumen suitable for draining blood from the SVC, right atrium, and/or right ventricle of a patient, and the second tube comprises a lumen suitable for returning oxygenated blood from a lung assist device to the pulmonary artery of the patient; (120) inserting the catheter into the patient such that the end of the first tube is located in the patient's right ventricle, and a portion of the first tube having openings for draining blood is located in the SVC, right atrium, and/or right ventricle, and such that the second tube, which is connected to the first tube, is fed through the tricuspid valve, through the right ventricle, through the pulmonary valve, and into the pulmonary artery, wherein the portion of the second tube having openings, i.e., the end of the second tube, is located in the pulmonary artery; and (130) connecting the catheter to a lung assist device such that un-oxygenated blood is removed from the patient's SVC, right atrium, and/or right ventricle via the first tube, and oxygenated blood is returned to the patient's pulmonary artery via the second tube. In one embodiment, the method comprises the step of inserting the catheter using a guidance mechanism, for example, but not limited to, a guide wire or X-ray guidance system (125). In one embodiment, the patient's blood is oxygenated via an ECMO or other lung assist device.

The disclosures of each and every patent, patent application, and publication cited herein are hereby incorporated herein by reference in their entirety. While this invention has been disclosed with reference to specific embodiments, it is apparent that other embodiments and variations of this invention may be devised by others skilled in the art without departing from the true spirit and scope of the invention. The appended claims are intended to be construed to include all such embodiments and equivalent variations.

Claims

Attorney Docket No.: 206030-0050-00- WO.604365 CLAIMS What is claimed is:

1. A catheter for use with a lung assist device, comprising:

a first tube having a lumen with at least one opening to the lumen suitable for draining substantially un-oxygenated blood from a patient and transferring the drained blood to the lung assist device; and

a second tube having a lumen with at least one opening to the lumen suitable for returning oxygenated blood to the patient;

wherein at least one of the openings of the first tube is positioned along the length of the first tube such that the opening is positioned in the patient's right ventricle when inserted into a patient, and wherein at least one of the openings of the second tube is positioned along the length of the second tube such that the opening is positioned in the patient's pulmonary artery when inserted into the patient.

2. The catheter of claim 1, wherein at least one of the openings of the first tube is positioned along the length of the first tube such that the opening is positioned in the patient's superior vena cava when inserted into the patient.

3. The catheter of claim 1, wherein at least one of the openings of the first tube is positioned along the length of the first tube such that the opening is positioned in the patient's right atrium when inserted into the patient.

4. The catheter of claim 1 , wherein the catheter is sized for blood flow in the range of about 3 to 4 L per minute.

5. The catheter of claim 1, wherein at least a portion of the first tube is reinforced with wire.

6. The catheter of claim 1, wherein at least a portion of the second tube is reinforced with wire.

7. A method for oxygenating blood in a subject, comprising:

inserting a catheter comprising a first tube and a second tube into a subject, such that the catheter enters the subject's heart via the superior vena cava, passes through the right atrium and right ventricle, and extends into the pulmonary artery;

draining blood from the subject's right ventricle via the first tube;

oxygenating the drained blood; and

returning the oxygenated blood to the subject's pulmonary artery via the second tube.

8. The method of claim 7, wherein the first and second tubes run substantially parallel to each other along at least a portion of the length of the catheter.

9. The method of claim 7, wherein the first tube and second tube are coaxial along at least a portion of the length of the catheter.

10. The method of claim 7, wherein blood is also drained from the subject's superior vena cava via the first tube.

11. The method of claim 7, wherein blood is also drained from the subject's right atrium via the first tube.

12. The method of claim 7, wherein the blood is oxygenated using an extra-corporeal membrane oxygenation (ECMO) device.

13. The method of claim 7, wherein the catheter is inserted into the subject using guiding mechanism.

14. The method of claim 13, wherein the guiding mechanism is a guide wire.

15. The method of claim 13, wherein the guiding mechanism is an X-ray guidance system.

16. A portable system for extracorporeal membrane oxygenation, comprising: an oxygenator, having a first chamber and a second chamber, the first chamber having an inlet and an outlet, the second chamber having an inlet and an outlet, and a membrane separating the first chamber and the second chamber;

a means for supplying a sweep gas to the inlet of the first chamber of the oxygenator;

a catheter, having a first lumen and a second lumen; and

a pump;

wherein the first lumen is connected to the pump, the pump is connected to the inlet of the second chamber of the oxygenator via a third lumen, and the second lumen is connected to the outlet of the second chamber of the oxygenator;

wherein when the first lumen and second lumen are also connected to a blood vessel of a subject, blood can flow from the subject through the first lumen, through the pump, through the third lumen, through the second chamber of the oxygenator, and through the second lumen back into the subject; and

wherein the subject's blood can be oxygenated via transfer of oxygen across the membrane in the oxygenator.

17. The system of claim 16, wherein the sweep gas is air.

18. The system of claim 16, wherein at least a portion of the catheter is surgically implantable.

19. The system of claim 16, wherein the means for supplying a sweep gas to the oxygenator is a fan.

20. The system of claim 16, wherein the pump is a centrifugal pump.

21. The system of claim 16, wherein the pump is an axial pump.

22. The system of claim 16, further comprising an air filter for filtering the sweep gas.

23. The system of claim 16, further comprising a power source.

24. The system of claim 16, further comprising a flow sensor for measuring the rate of blood flow through the device.

25. The system of claim 16, further comprising at least one sensor for measuring the oxygenation level of blood in the device.

26. The system of claim 16, wherein at least one lumen of the catheter is inserted into the subject's pulmonary artery.