Perfusion system

• US 6,287,273 B1
• Filed: 07/20/1999
• Issued: 09/11/2001
• Est. Priority Date: 07/10/1999
• Status: Expired due to Fees

• Current Assignee: Argmed Kommanditbolag
• Original Assignee: Argmed Kommanditbolag
• Inventors: Jeppson, Bengt, Ivancev, Krasnodar, Allers, Mats
• Primary Examiner(s): MENDEZ, MANUEL A
• Application Number:
  US09/357,124
• Time in Patent Office: 784 Days
• Field of Search: 604/4.01, 604/35, 604/28, 604/43, 604/27, 604/96.01, 604/97.01, 604/97.03, 604/98.01, 604/101.01, 604/101.02, 604/101.03, 604/101.04, 604/101.05, 604/102-1-1, 604/171, 604/192, 604/194, 606/191-194
• US Class Current: 604/27
• CPC Class Codes: A61M 1/3613 Reperfusion, e.g. of the coronary vessels, e.g. retroperfusion
• CPC Class Codes: A61M 1/3615 Cleaning blood contaminated by local chemotherapy of a body part temporarily isolated from the blood circuit
• CPC Class Codes: A61M 1/3621 Extra-corporeal blood circuits single-needle circuits A61M1/30
• CPC Class Codes: A61M 2025/1052 for temporarily occluding a vessel for isolating a sector
• CPC Class Codes: A61M 2025/1095 with perfusion means for enabling blood circulation while the balloon is in an inflated state or in a deflated state, e.g. permanent by-pass within catheter shaft
• CPC Class Codes: A61M 2210/1071 Liver; Hepar
• CPC Class Codes: A61M 25/1011 Multiple balloon catheters

Abstract

A perfusion system for non-surgically isolating and perfusing an organ, particularly the liver (101), in a patient, and including; by-pass cathether apparatus having inlet and outlet lumens (111, 112) introducible into the blood vessels of the organ percutaneously and devised so as to by-pass the blood flow past the organ in a by-pass circuit; perfusion catheter apparatus having inlet and outlet lumens (114, 116) introducible into the blood vessels percutaneously and being devised so as to lead the flow of perfusion fluid in a perfusion circuit through the organ; occlusive seals (106, 108) for isolating the organ from the systemic blood flow; pump apparatus including a by-pass pump (261), a perfusion fluid pump (124) and a suction pump (134) for establishing a negative relative pressure at the perfusion outlet from the organ; and control apparatus (128) coupled to the pumps (124, 126, 134) so as to control the operation thereof such that the outflow of fluid from the organ exceeds the inflow of fluid into the organ in the perfusion circuit due to a net volume contribution of blood from the systemic circulation entering the isolated organ.

Claims

1. A perfusion system for non-surgically isolating and perfusing an organ in the body of a living being with a perfusion fluid, comprising:

a set of catheters including,

(1) bypass catheter means having inlet and outlet conduits and being percutaneously introducible into the main inflow and outflow, blood vessels of the organ and being devised to lead the systemic blood flow past the organ in a partially extracorporeal bypass circuit;

(2) perfusion catheter means having inlet and outlet conduits being percutaneously introducible into the main inflow and outflow blood vessels of the organ and being devised to lead the flow of perfusion fluid through the organ in a partially extra-corporeal perfusion circuit; and

(3) occlusive seals being percutaneously introducible between distal end openings of the bypass conduits and the perfusion conduits in the main inflow and outflow blood vessels and being devised to seal off the main blood inflow and outflow of said organ such that the occlusive seals separate the bypass circuit from the perfusion circuit.

2. The perfusion system of claim 1, wherein the catheter means of said set of catheters includes:

(a) a first catheter, having a perfusion lumen with distal and proximal end openings and an occlusive seal, said distal end opening being positioned distally of the occlusive seal;

(b) a second catheter, having a bypass lumen with distal and proximal end openings and an occlusive seal, said distal end opening being positioned proximally of the occlusive seal;

(c) a third catheter with an introducer, having an introducer lumen with distal and proximal end openings and being devised to operate as a perfusion lumen, said catheter having a bypass lumen with distal and proximal end openings and an occlusive seal, said third catheter being devised such that the occlusive seal is positioned between said distal end opening of the bypass lumen and said distal end opening of the introducer lumen during operation of the system;

(d) a fourth catheter, having a perfusion inlet lumen with distal and proximal end openings and an occlusive seal, said distal end opening being positioned distally of the occlusive seal; and

(e) a fifth catheter, having a bypass lumen with distal and proximal end openings.

3. The perfusion system of claim 2, wherein the catheter means of said set of catheters is devised for isolating and perfusing the liver of a living being and:

(a) the first catheter is devised to be placed in vena cava inferior by means of an introducer having a maximum outer diameter of 14 French, the occlusive seal of said first catheter being capable to efficiently seal off vena cava inferior upstream the hepatic veins;

(b) the second catheter is devised to be placed in vena cava inferior by means of an introducer having a maximum outer diameter of 14 French, the occlusive seal of said second catheter being capable to efficiently seal off vena cava inferior between the hepatic veins and the heart;

(c) the third catheter is devised to be placed percutaneously and trans hepatically in vena porta by means of an introducer with a maximum outer diameter of 12 French, the occlusive seal of said third catheter being capable to efficiently seal off vena porta; and

(d) the fourth catheter is devised to be placed in the hepatic artery by means of an introducer with a maximum outer diameter of 5 French, the occlusive seal of said fourth catheter being capable to efficiently seal off the hepatic artery.

4. The perfusion system of claim 1, wherein the catheter means of said set of catheters includes;

(a) a first catheter, having a perfusion lumen with distal and proximal end openings and a first occlusive seal being positioned distally of said distal end opening and a second occlusive seal being positioned proximally of said distal end opening;

(b) a second catheter, having a bypass lumen with distal and proximal end openings;

(c) a third catheter with an introducer, having an introducer lumen with distal and proximal end openings and being devised to operate as a perfusion lumen, said catheter having a bypass lumen with distal and proximal end openings and an occlusive seal, said third catheter being devised such that the occlusive seal is positioned between said distal end opening of the bypass lumen and said distal end opening of the introducer lumen during operation of the system;

(d) a fourth catheter, having a perfusion inlet lumen with distal and proximal end openings and an occlusive seal, said distal end opening being positioned distally of the occlusive seal; and

(e) a fifth catheter, having a bypass lumen with distal and proximal end openings.

5. The perfusion system of claim 4, wherein the catheter means of said set of catheters is devised for isolating and perfusing the liver of a living being and:

(a) the first catheter is devised to be placed in vena cava inferior by means of an introducer having a maximum outer diameter of 14 French, the first occlusive seal of said first catheter being capable to efficiently seal off vena cava inferior between the heart and the hepatic veins, and the second occlusive seal of said first catheter being capable to efficiently seal off vena cava inferior below the hepatic veins;

(b) the second catheter is devised to be placed in vena cava inferior by means of an introducer having a maximum outer diameter of 14 French;

(c) the third catheter is devised to be placed percutaneously and trans hepatically in vena porta by means of an introducer with a maximum outer diameter of 12 French, the occlusive seal of said third catheter being capable to efficiently seal off vena porta; and

(d) the fourth catheter is devised to be placed in the hepatic artery by means of an introducer with a maximum outer diameter of 5 French, the occlusive seal of said fourth catheter being capable to efficiently seat off the hepatic artery.

6. The perfusion system of claim 1 further comprising:

(4) a pump apparatus for maintaining a flow in said bypass and perfusion circuits, said pump apparatus having;

(a) a bypass pump, which is couplable to the extracorporeal parts of the bypass circuit, for pumping the blood in said bypass circuit, for pumping the blood in said bypass circuit;

(b) a perfusion pump, which is couplable to the extracorporeal part of the perfusion circuit, for pumping a perfusion fluid in said perfusion circuit; and

(c) means for establishing a negative relative pressure at the distal end of the perfusion outlet conduit; and

(5) a perfusion control apparatus, which is couplable to said pump apparatus and devised to control the operation of said pump apparatus such that the outflow of fluid from the organ exceeds the inflow of fluid into the organ in the perfusion circuit due to a net volume contribution of blood from the systemic circulation entering the isolated organ.

7. The system of claim 6, further comprising a perfusion reservoir devised to be connectable to the extra-corporeal part of the perfusion circuit such that a perfusion fluid in the perfusion circuit passes through the reservoir.

8. The system of claim 7, wherein the perfusion reservoir is devised to enable vertical movement of the reservoir for establishing mid controlling a negative relative pressure at a distal end opening of a perfusion outlet conduit.

9. The system of claim 7, further comprising a vacuum source being connectable to the perfusion reservoir and devised for establishing and controlling a negative relative pressure at a distal end opening of a perfusion outlet conduit.

10. The system of claim 7, further comprising a suction pump being connectable to the extra-corporeal part of the perfusion circuit and devised for establishing a negative relative pressure at a distal end opening of a perfusion outlet conduit.

11. The system of claim 6, further comprising:

a heating equipment devised to heat a perfusion fluid in the perfusion circuit; and

an oxygenator devised to oxygenate a perfusion fluid in the perfusion circuit.

12. The system of claim 1, further comprising means for exchanging a first perfusion fluid with a second perfusion fluid during operation of the system.

13. The system of claim 6, further comprising a leakage indicating substance devised to be added to a perfusion fluid for enabling detection of leakage to the systemic blood circulation during operation of the system.

14. The system of claim 6, further comprising a fluid exchange substance devised to be added to a perfusion fluid for enabling monitoring and control of the exchange of a first perfusion fluid with a second perfusion fluid during operation of the system.

15. The system of claim 6, wherein the bypass inlet and outlet conduits and the perfusion inlet and outlet conduits are lumens of catheters.

16. The system of claim 6, wherein the bypass inlet and outlet conduits and the perfusion inlet and outlet conduits are lumens of catheter introducers.

17. The system of claim 6, wherein the occlusive seals are occlusion balloons of balloon catheters.

18. The system of claim 6, wherein the organ of the living being, which is connected to the perfusion circuit, is a liver.

19. The perfusion system of claim 1 further comprising,

(4) a pump apparatus having:

(a) a first pump which is couplable to an extracorporeal conduit of a bypass circuit though which the systemic blood circulation is bypassed an essentially isolated organ;

(b) a second pump which is couplable to an extracorporeal conduit of a perfusion circuit, through which circuit a perfusion fluid perfuses the essentially isolated organ;

(c) means for establishing negative relative pressure at the distal end of the perfusion outlet conduit;

(d) a perfusion reservoir, which is connectable into the perfusion circuit between the outlet from the essentially isolated organ and the second pump, and to which a drug supply is connectable; and

whereby an essentially isolated organ can be connected to a perfusion circuit with circulating perfusion fluid, and the natural bloodstream is bypassed past said organ through a bypass circuit, said circuits being connected to the perfusion apparatus.

20. The perfusion system of claim 1 further comprising:

(4) a control apparatus for controlling the perfusion of an organ in the body of a living being with a perfusion fluid, including;

(a) pressure control device, to control blood pressures and pressure of a perfusion fluid in a perfusion circuit;

(b) a temperature control device, to control temperatures in the body of a living being in the perfusion fluid; and

(c) a flow rate control device to, control flow rates in the perfusion circuit and a bypass circuit;

the control apparatus being couplable to said perfusion pump apparatus.

21. The perfusion system of claim 20, wherein the control apparatus further comprises a level control device, to control the level in a perfusion reservoir of a perfusion apparatus.

22. The perfusion system of claim 20 wherein the control apparatus further comprises a device for controlling an automated valve between a perfusion reservoir and a reservoir for fresh blood being couplable to an extra-corporeal perfusion circuit and being devised to switch between the perfusion reservoir and the reservoir in case of a detected leakage from the perfusion circuit to the systemic blood circulation.

23. A method for non-surgically essentially isolating and perfusing an organ in a body of a living being, comprising the steps of:

(a) sealing off the main input and output blood vessels of said organ by means of percutaneously introducing seals in said main blood vessels, such that said organ becomes essentially isolated from the systemic blood circulation;

(b) establishing a bypass circuit by means of percutaneously introducing bypass conduits having distal and proximal ends with openings, placing the distal ends in the main input and output blood vessels of said organ and connecting the proximal ends by an extracorporeal conduit, through which bypass circuit the systemic blood is bypassed past said organ;

(c) establishing a perfusion circuit by means of percutaneously introducing perfusion conduits having distal and proximal ends with openings, placing the distal ends in the main input and output blood vessels of said organ and connecting tie proximal ends by an extracorporeal conduit, into which perfusion circuit the organ is connected;

(d) circulating a perfusion fluid in said perfusion circuit so that the perfusion fluid perfuses the organ.

24. The method of claim 23, further comprising the step of:

establishing a negative pressure at the distal end of a perfusion conduit said perfusion conduit being the outlet from the organ into the perfusion circuit, such that the outflow of said organ is slightly higher than the inflow from the perfusion circuit,

whereby the perfusion fluid is supplied with a net volume contribution of blood from the systemic circulation entering the essentially isolated organ.

25. The method of claim 23, wherein the step of sealing off the main input and output blood vessels comprises:

(a) percutaneously placing occlusive seals in main output blood vessels of said organ for enabling the main blood flow out from said organ to be sealed off;

(b) percutaneously placing occlusive seals in main input blood vessels for enabling the main blood flow in to said organ to be sealed off; and

(c) sealing off the blood inflow and outflow of said organ, by means of said occlusive seals, such that the organ is essentially isolated from the systemic blood circulation.

26. The method of claim 23, wherein the step of establishing a bypass circuit comprises:

(a) percutaneously introducing bypass inlet and bypass outlet conduits having a distal and a proximal ends with openings, such that the distal end openings of said conduits are positioned in main blood vessels on the outside, compared to the organ, of the occlusive seals for sealing off the main organ output and input blood vessels; and

(b) connecting the proximal end openings of said bypass inlet and outlet conduits through conduits to an partially extracorporeal bypass circuit.

27. The method of claim 23, wherein the step of establishing a perfusion circuit comprises:

(a) percutaneously placing perfusion inlet and perfusion outlet conduits having a distal and a proximal ends with openings, such that the distal end openings of said conduits are positioned in main blood vessels on the organ side of the occlusive seals for sealing off the main organ output and input blood vessels; and

(b) connecting the proximal end openings of said perfusion inlet and outlet conduits to an extracorporeal perfusion circuit.

28. The method of claim 23, further comprising the step of:

circulating the systemic blood past said organ in the bypass circuit.

29. The method of claim 23, further comprising the step of:

adding drugs to the perfusion fluid in the perfusion circuit so that it perfuses through the organ.

30. The method of claim 23, wherein the placing of occlusive seals, perfusion conduits and bypass conduits is performed by the placing of percutaneously introducible catheters.

31. The method of claim 23, wherein the perfused organ is a liver in the body of a living being.

32. The method of claim 23, wherein the pension is performed in retrograde such that a perfusion inlet lumen is placed such that the distal end opening is positioned in a blood vessel with the normal blood flow out from the organ and a perfusion outlet lumen is placed such that its distal end opening is positioned in a blood vessel with the normal blood flow in to the organ.

33. A method for non-surgically isolating and perfusing a liver in the body of a living being without using surgery, comprising the steps of:

(a) placing, percutaneously, a first catheter, having a lumen with distal and proximal end openings and an occlusive seal, in the inferior vena cava of the patient such that the seal is positioned upstream the liver and he distal end openings of the lumen is positioned downstream said occlusive seal;

(b) placing, percutaneously, a second catheter, having a lumen with distal and proximal end openings and an occlusive seal, in the inferior vena cava of the patient such that the seal is positioned downstream the vena hepatica and the distal end openings of the lumen is positioned downstream of said occlusive seal;

(c) placing, percutaneously and trans-hepatically, a third catheter by mean of an introducer, having an introducer lumen with distal and proximal end openings, the catheter having a lumen with distal and proximal end openings and an occlusive seal, in the vena porta of the patient such that the distal end openings of the lumen is positioned upstream the distal end openings of the introducer lumen and the seal is positioned between the distal end openings of said introducer lumen and said lumen;

(d) placing a fourth catheter, having a lumen with distal and proximal end openings and an occlusive seal, in the hepatic artery of the patient such that the distal end openings of the lumen is positioned downstream said occlusive seal;

(e) placing a fifth catheter, having a lumen with distal and proximal end openings, in the inferior vena cava, such that the distal end opening of said lumen ends upstream of the occlusive seal of said first catheter;

(f) connecting the proximal ends openings of the lumens of the third and the fifth catheters with the proximal end openings of the lumen of the second catheter, such that a partially extracorporeal bypass circuit is formed;

(g) connecting the proximal end opening of the introducer lumen of said introducer for the third catheter with the proximal end openings of the lumens of the first and the fourth catheters, such that a partially extracorporeal perfusion circuit is formed;

(h) sealing off the flow of blood past the occlusive seal in the inferior vena cava with said seal of said first catheter;

(i) sealing off the flow of blood past the occlusive seal in the inferior vena cava with said seal of said second catheter;

(j) sealing off the flow of blood past the occlusive seal in the vena porta with the said seal of said third catheter;

(k) sealing off the flow of blood past the seal in the arteria hepatica with said seal of said fourth catheter;

(l) circulating the blood past said organ in said bypass circuit;

(m) establishing a negative relative pressure at the distal end of the perfusion outlet lumen; and

(n) circulating a perfusion fluid in said perfusion circuit so that the perfusion fluid perfuses the organ, such that the outflow of said organ is equal to or slightly higher than the inflow and the perfusion fluid is supplied with a net volume contribution of blood from the systemic circulation entering the essentially isolated organ.

34. A method for non-surgically isolating and perfusing a liver in the body of a living, being without using surgery, comprising the steps of:

(a) placing, percutaneously, a first catheter, having a lumen with distal and proximal end openings and a first and a second occlusive seal, in he inferior vena cava of the patient such that the first occlusive seal is positioned between the heart and the hepatic veins, the second occlusive seal is positioned downstream the hepatic veins, and the distal end openings of the lumen is positioned between said first occlusive seal and second occlusive seal;

(b) placing, percutaneously, a second catheter, having a lumen with distal and proximal end openings, in the inferior vena cava of the patient such that the distal end opening is positioned between the heart and said first occlusive seal of the first catheter;

(c) placing, percutaneously and trans-hepatically, a third catheter by means of an introducer, having an introducer lumen with distal and proximal end openings, the catheter having a lumen with distal and proximal end openings and an occlusive seal, in the vena porta of the patient such that die distal end openings of he lumen is positioned upstream the distal end openings of the introducer lumen and the seal is positioned between the distal end openings of said introducer lumen and said lumen;

(d) placing a fourth catheter, having a lumen with distal and proximal end openings and an occlusive seal, in the hepatic artery of the patient such that the distal end openings of the lumen is positioned downstream said occlusive seal;

(e) placing a fifth catheter, having a lumen with distal and proximal end openings, in the inferior vena cava, such that the distal end opening of said lumen ends upstream of said second occlusive seal of said first catheter;

(f) connecting the proximal ends openings of the lumens of the third and the fifth catheters with the proximal end openings of the lumen of the second catheter, such that a partially extracorporeal bypass circuit is formed;

(g) connecting the proximal end opening of the introducer lumen of said introducer for the third catheter with the proximal end openings of the lumens of the first and the fourth catheters, such that a partially extracorporeal perfusion circuit is formed;

(h) sealing off the flow of blood past the occlusive seal in the inferior vena cava with said seal of said first catheter;

(i) sealing off the flow of blood past the occlusive seal in the inferior vena cava with said seal of said second catheter;

(j) sealing off the flow of blood past the occlusive seal in the vena porta with the said seal of said third catheter;

(k) sealing off the flow of blood past the seal in the arteria hepatica with said seal of said fourth catheter,

(l) circulating the blood past said organ in said bypass circuit;

(m) establishing a negative relative pressure at the distal end of the perfusion outlet lumen; and

(n) circulating a perfusion fluid in said perfusion circuit so that the perfusion fluid perfuses the organ such that the outflow of said organ is equal to or slightly higher than the inflow and the perfusion fluid is supplied with a net volume contribution of blood from the systemic circulation entering the essentially isolated organ.