Hemostatic system and components for extracorporeal circuit

• US 6,733,471 B1
• Filed: 09/15/2000
• Issued: 05/11/2004
• Est. Priority Date: 03/16/1998
• Status: Expired due to Term

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Ericson, Daniel G., Thor, Eric J., Haworth, William S.
• Primary Examiner(s): Bianco, Patricia
• Application Number:
  US09/662,044
• Time in Patent Office: 1,334 Days
• Field of Search: 604/4.01, 604/6.01, 604/5-1-, 604/6.09, 604/6.16, 604/19, 604/27, 604/28, 604/65-67, 604/500, 604/503, 604/504, 128/DIG.3, 128/898, 422/44-48, 210/645-47, 210/650-51, 210/739, 210/743, 210/767, 210/746, 210/85, 210/96-- 9, 210/198.1, 210/321.6, 210/348, 210/418, 210/929, 600/300-1, 600/309, 600/310, 600/314, 600/316, 600/322-24, 600/326, 600/334, 600/347-48, 600/352, 600/361, 600/366-69, 600/437-39, 600/459, 600/466-68, 600/504-5
• US Class Current: 604/4.01
• CPC Class Codes: A61M 1/3609 Physical characteristics of the blood, e.g. haematocrit, urea
• CPC Class Codes: A61M 1/3623 Means for actively controlling temperature of blood
• CPC Class Codes: A61M 1/3666 Cardiac or cardiopulmonary bypass, e.g. heart-lung machines
• CPC Class Codes: A61M 1/367 Circuit parts not covered by the preceding subgroups of group A61M1/3621
• CPC Class Codes: A61M 1/3672 Means preventing coagulation
• CPC Class Codes: A61M 1/3673 Anticoagulant coating, e.g. Heparin coating
• CPC Class Codes: A61M 1/3675 Deactivation
• CPC Class Codes: A61M 2202/0478 Heparin
• CPC Class Codes: B01D 2325/16 Membrane materials having positively charged functional groups
• CPC Class Codes: Y10S 128/03 Heart-lung

Abstract

A method and system for use in the course of extracorporeal blood flow, e.g., cardiopulmonary bypass, dialysis, and angioplasty procedures, in order to reduce or minimize inflammation, excessive bleeding, and other undesirable side effects. The system can include one or more automated blood parameter sensor modules and one or more blood parameter regulating modules. The system is particularly well suited to monitor and/or regulate blood parameters that include blood analytes (e.g., biomolecules, drugs or metabolites) as well as blood functions (e.g., clotting time, fibrinolytic activity, immune response). The system is particularly well suited for use in the management of clotting (e.g., heparing/protamine) and bleeding (e.g., aprotinin).

Claims

1. A system for use in combination with an extracorporeal blood flow circuit, the system comprising:

a) one or more automated sensor modules adapted to monitor, directly or indirectly, the presence of one or more blood parameters, and

b) one or more regulating modules adapted to affect the presence, concentration and/or activity of one or more blood parameters, wherein the system comprises at least one sensor module that is adapted to incorporate flow injection analysis (“

FIA”

) techniques, and that comprises;

i) a blood withdrawal component with in-line access, ii) an analytical component, and iii) a readout component.

2. A system according to claim 1 wherein the monitored blood parameter and the regulated blood parameter are the same.

3. A system according to claim 1 wherein the blood parameter is selected from the group consisting of blood analytes and blood functions.

4. A system according to claim 3 wherein the blood analytes are selected from the group consisting of biomolecules, drugs and metabolites, and the blood functions are selected from the group consisting of clotting time, fibrinolytic activity, and immune response.

5. A system according to claim 4 wherein the blood analytes comprise heparin concentration and aprotinin concentration, and the blood functions comprise clotting time.

6. A system according to claim 1 wherein the sensor module provides semicontinuous and/or continuous sampling of the blood, in order to provide substantially real-time digital output readings of the monitored parameter.

7. A system according to claim 1 wherein the regulating modules comprise a filter adapted to remove inflammation mediators from the blood, the filter providing a support surface selected from the group consisting of a specific binding ligand or hydrophobic surface.

8. A system according to claim 7 wherein the inflammation mediators are selected from the group consisting of anaphylatoxins, chemokines, and proinflammatory cytokines, and the support surface comprises a hydrophobic surface selected from the group consisting of acrylic polymers selected from the group consisting of acrylonitrile polymers, copolymers and polymer blends;

polysulfones;

polyamides selected from the group consisting of Nylon-6, Nylon-6,6, Nylon-11, Nylon-12, Nylon 6,9, Nylon-12; and

acrylic and methacrylic ester polymers.

9. A system according to claim 1 comprising a regulating module adapted to remove heparin from the blood stream by anionic exchange of heparin with an immobilized positively charged species on the surface of a membrane.

10. A system according to claim 1 wherein at least one regulating module comprises a filter for the extracorporeal removal of heparin from the blood stream.

11. A system according to claim 10 wherein the removal of heparin is accomplished by anionic exchange of heparin with an immobilized positively charged species on the surface of a membrane contained within the filter.

12. A system according to claim 11 wherein the species are selected from charged amino acids or a charged material surface.

13. A system according to claim 10 wherein the heparin filter comprises a material interface having affinity for heparin.

14. A system according to claim 13 wherein the material comprises either charged amino acids or a charged material surface.

15. A system according to claim 14 wherein the capacity of the heparin filter material is increased by the use of using a sandwich surface treatment procedure in which layers of a plurality of polymers are provided upon the material.

16. A system according to claim 15 wherein the polymers comprise polyethylimmine (Polymer A) and a hydrogel polymer (Polymer B).

17. A system according to claim 16 wherein the layers comprise a sandwich in the form of Polymer A+Polymer B+Polymer A upon the material surface.

18. A system according to claim 1, wherein at least one regulating module comprises an inflammation filter comprising a hydrophobic surface positioned within a flow chamber having blood inlet and blood outlet ports.

19. A system according to claim 18, wherein the inflammation filter is a complement filter.

20. A system according to claim 1 wherein at least one regulating module comprises a heparin filter in the form of a mass transfer device having a microporous hollow fiber bundle.

21. A system according to claim 20 wherein the mass transfer device comprises a hollow fiber bundle wound on a supporting core for radially outward flow of a first fluid.

22. A system according to claim 21 wherein the heparin filter is adapted to to remove enough heparin to effectively de-heparinize a fully anticoagulated patient.

23. A system according to claim 22 wherein the heparin filter can remove on the order of 20,000 units of heparin within 5-15 minutes.

24. A system according to claim 20 wherein the heparin filter is incorporated within the circuit of a conventional CPB system.

25. A system according to claim 24 wherein the filter is provided as a shunt between between the flow path between a CPB reservoir and the right atrium of the heart, and the flow path between the CPB oxygenator and the aorta.

26. A system according to claim 25 wherein both flow paths are adapted to being clamped off distally at points beyond the shunt path junction points.

27. A system according to claim 1 further comprising a system for performing automated sequential injection analysis (SIA) of a plurality of blood parameters or samples.

28. A system according to claim 1 wherein the flow injection analysis further comprises the use of a flow cell and spectrophotometer.

29. A system according to claim 1 wherein the monitoring of blood parameters comprises the use of fiber-optic measurements.

58. A method according to claim 11 comprising a regulating module adapted to remove heparin from the blood stream by anionic exchange of heparin with an immobilized positively charged species on the surface of a membrane.

30. A method for monitoring and regulating blood parameters in the course of extracorporeal blood flow, the method comprising:

a) providing an extracoporeal blood flow circuit comprising, in the order of blood flow, a reservoir, a pump, and oxygenator, a filter, together with associated tubing, connectors and controls,

b) providing a system comprising

i) one or more automated sensor modules adapted to monitor, directly or indirectly, the presence of one or more blood parameters, and

ii) one or more regulating modules adapted to affect the presence, concentration and/or activity of one or more blood parameters.

c) employing the sensor module(s) to monitor one or more blood parameters, and

d) employing the filter module(s) to affect the presence, concentration and/or activity of one or more blood components, wherein the system comprises at least one sensor module that is adapted to incorporate flow injection analysis (“

FIA”

) techniques, and that comprises;

i) a blood withdrawal component with in-line access, ii) an analytical component, and iii) a readout component.

31. A method according to claim 30 wherein the monitored blood parameter and the regulated blood parameter are the same.

32. A method according to claim 30 wherein the blood parameter is selected from the group consisting of blood analytes and blood functions.

33. A method according to claim 32 wherein the blood analytes are selected from the group consisting of biomolecules, drugs and metabolites, and the blood functions are selected from the group consisting of clotting time, fibrinolytic activity, and immune response.

34. A method according to claim 33 wherein the blood analytes comprise heparin concentration and aprotinin concentration, and the blood functions comprise clotting time.

35. A method according to claim 30 wherein the sensor module provides semicontinuous and/or continuous sampling of the blood, in order to provide substantially real-time digital output readings of the monitored parameter.

36. A method according to claim 30 wherein the regulating modules comprise a filter adapted to remove inflammation mediators from the blood, the filter providing a support surface selected from the group consisting of a specific binding ligand or hydrophobic surface.

37. A method according to claim 36 wherein the inflammation mediators are selected from the group consisting of anaphylatoxins, chemokines, and proinflammatory cytokines, and the support surface comprises a hydrophobic surface selected from the group consisting of acrylic polymers selected from the group consisting of acrylonitrile polymers, copolymers and polymer blends;

polysulfones;

polyamides selected from the group consisting of Nylon-6, Nylon-6,6, Nylon-11, Nylon-12, Nylon 6,9, Nylon-12; and

acrylic and methacrylic ester polymers.

38. A method according to claim 30 wherein at least one regulating module comprises a filter for the extracorporeal removal of heparin from the blood stream.

39. A method according to claim 38 wherein the removal of heparin is accomplished by anionic exchange of heparin with an immobilized positively charged species on the surface of a membrane contained within the filter.

40. A method according to claim 39 wherein the species are selected from charged amino acids or a charged material surface.

41. A method according to claim 38 wherein the heparin filter comprises a material interface having affinity for heparin.

42. A method according to claim 41 wherein the material comprises either charged amino acids or a charged material surface.

43. A method according to claim 42 wherein the capacity of the heparin filter material is increased by the use of using a sandwich surface treatment procedure in which layers of a plurality of polymers are provided upon the material.

44. A method according to claim 43 wherein the polymers comprise polyethylimmine (Polymer A) and a hydrogel polymer (Polymer B).

45. A method according to claim 44 wherein the layers comprise a sandwich in the form of Polymer A+Polymer B+Polymer A upon the material surface.

46. A method according to claim 30, wherein at least one regulating module comprises an inflammation filter comprising a hydrophobic surface positioned within a flow chamber having blood inlet and blood outlet ports.

47. A method according to claim 46, wherein the inflammation filter is a complement filter.

48. A method according to claim 30 wherein at least one regulating module comprises a heparin filter in the form of a mass transfer device having a microporous hollow fiber bundle.

49. A method according to claim 48 wherein the mass transfer device comprises a hollow fiber bundle wound on a supporting core for radially outward flow of a first fluid.

50. A method according to claim 49 wherein the heparin filter is adapted to to remove enough heparin to effectively de-heparinize a fully anticoagulated patient.

51. A method according to claim 50 wherein the heparin filter can remove on the order of 20,000 units of heparin within 5-15 minutes.

52. A method according to claim 30 further comprising a system for performing automated sequential injection analysis (SIA) of a plurality of blood parameters or samples.

53. A method according to claim 30 wherein the flow injection analysis further comprises the use of a flow cell and spectrophotometer.

54. A method according to claim 30 wherein the monitoring of blood parameters comprises the use of fiber-optic measurements.

55. A method according to claim 46 wherein the heparin filter is incorporated within the circuit of a conventional CPB system.

56. A method according to claim 55 wherein the filter is provided as a shunt between between the flow path between a CPB reservoir and the right atrium of the heart, and the flow path between the CPB oxygenator and the aorta.

57. A method according to claim 56 wherein both flow paths are adapted to being clamped off distally at points beyond the shunt path junction points.