Reduction of postoperative complications of cardiopulmonary bypass (CPB) surgery

• US 6,641,571 B2
• Filed: 01/04/2001
• Issued: 11/04/2003
• Est. Priority Date: 01/05/2000
• Status: Active Grant

• Current Assignee: ED. Geistlich Soehne AG Fuer Chemische Industrie
• Original Assignee: ED. Geistlich Soehne AG Fuer Chemische Industrie
• Inventors: Redmond, H. Paul, Pfirrmann, Rolf W.
• Primary Examiner(s): Look, Edward K.
• Assistant Examiner(s): FRISTOE JR, JOHN K
• Application Number:
  US09/753,719
• Publication Number:
  US 20020035996A1
• Time in Patent Office: 1,034 Days
• Field of Search: 604/500, 604/507, 604/508, 604/509, 128/898
• US Class Current: 604/508
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/549 having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 39/00 General protective or antinoxious agents
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Patients undergoing cardiopulmonary bypass surgery are treated perioperatively with methylol transfer agents, such as Taurolidine. Patients undergoing crystalloid cardioplegia who are treated with taurolidine show reduced levels of IL-6 and increased levels of IL-10 when compared to crystalloid cardioplegia patients administered a placebo. Crystalloid cardioplegia patients administered Taurolidine also show reduced levels of IL-6 and increased levels of IL-10 when compared to blood cardioplegia patients who were administered Taurolidine.

Claims

1. A method of reducing postoperative complications including myocardium damage by reperfusion associated with cardiopulmonary bypass (CPB) surgery in a patient, comprising administering to a patient an effective amount of a methylol transfer agent in conjunction with CPB surgery of said patient.

2. The method of claim 1 wherein said agent is selected from the group consisting of taurolidine, taurultam and mixtures thereof.

3. The method of claim 2 wherein said agent is administered to said patient during a time period selected from the group consisting of prior to said CPB surgery, during said CPB surgery, subsequent to said CPB surgery and combinations thereof.

4. The method of claim 2 wherein said agent comprises taurolidine solution.

5. The method of claim 4 wherein said solution is a 2% taurolidine solution.

6. The method of claim 5 wherein said taurolidine solution is administered to said patient at a dose of 250 mL.

7. The method of claim 6 wherein said patient receives two said doses per day at about 12 hour intervals following said surgery.

8. A method of reducing postoperative complications of cardiopulmonary bypass (CPB) surgery in a patient, comprising administering to a patient an effective amount of a methylol transfer agent in conjunction with CPB surgery of said patient, wherein said agent is administered to said patient so as to prevent or reduce elevation of IL-6 levels in said patient.

9. The method of claim 8 wherein said agent is selected from the group consisting of taurolidine, taurultam and mixtures thereof.

10. A method of reducing postoperative complications of cardiopulmonary bypass (CPB) surgery in a patient, comprising administering to a patient an effective amount of a methylol transfer agent in conjunction with CPB surgery of said patient, wherein said agent is administered to said patient so as to increase elevation or prevent reduction of IL-10 levels in said patient.

11. The method of claim 10 wherein said agent is selected from the group consisting of taurolidine, taurultam and mixtures thereof.

12. A method of reducing postoperative complications of cardiopulmonary bypass (CPB) surgery in a patient, comprising administering to a patient an effective amount of a methylol transfer agent in conjunction with CPB surgery of said patient, wherein said agent is administered to said patient so as to reduce or prevent systemic endotoxemia in said patient.

13. The method of claim 12 wherein said agent is selected from the group consisting of taurolidine, taurultam and mixtures thereof.

14. A method of reducing postoperative complications of cardiopulmonary bypass (CPB) surgery in a patient, comprising administering to a patient an effective amount of a methylol transfer agent in conjunction with CPB surgery of said patient, wherein said agent comprises a 2% taurolidine solution, wherein said taurolidine solution is administered to said patient at a dose of 250 mL, wherein said patient is administered said dose during said surgery.

15. A method of reducing postoperative complications of cardiopulmonary bypass (CPB) surgery in a patient, comprising administering to a patient an effective amount of a methylol transfer agent in conjunction with CPB surgery of said patient, wherein said patient is administered crystalloid cardioplegia.

16. A method of reducing postoperative complications including arrhythmia associated with cardiopulmonary bypass (CPB) surgery in a patient, comprising administering to a patient an effective amount of a methylol transfer agent in conjunction with CPB surgery of said patient.

17. The method of claim 16 wherein said agent is selected from the group consisting taurolidine, taurultam and mixtures thereof.

18. The method of claim 17 wherein said arrhythmia is sinus-arrhythmia.

19. A method of reducing postoperative complications including ventricular fibrillation associated with cardiopulmonary bypass (CPB) surgery in a patient, comprising administering to a patient an effective amount of a methylol transfer agent in conjunction with CPB surgery of said patient.

20. The method of claim 19 wherein said agent is selected from the group consisting of taurolidine, taurultam and mixtures thereof.

21. A method of reducing postoperative complications including heart fluttering associated with cardiopulmonary bypass (CPB) surgery in a patient, comprising administering to a patient an effective amount of a methylol transfer agent in conjunction with CPB surgery of said patient.

22. The method of claim 21 wherein said agent is selected from the group consisting of taurolidine, taurultam and mixtures thereof.

23. A method of reducing postoperative complications including cytokine activation associated with cardiopulmonary bypass (CPB) surgery in a patient, comprising administering to a patient an effective amount of a methylol transfer agent in conjunction with CPB surgery of said patient.

24. The method of claim 23 wherein said cytokine activation is ameliorated in a perioperative period.

25. The method of claim 24 wherein said agent is selected from the group consisting of taurolidine, taurultam and mixtures thereof.

26. A method of reducing postoperative complications including respiratory compromise associated with cardiopulmonary bypass (CPB) surgery in a patient, comprising administering to a patient an effective amount of a methylol transfer agent in conjunction with CPB surgery of said patient.

27. The method of claim 26, wherein said agent is selected from the group consisting of taurolidine, taurultam and mixtures thereof.

28. A method of reducing postoperative complications including ischemic reperfusion injury associated with cardiopulmonary bypass (CPB) surgery in a patient, comprising administering to a patient an effective amount of a methylol transfer agent in conjunction with CPB surgery of said patient.

29. The method of claim 28 wherein said agent is selected from the group consisting of taurolidine, taurultam and mixtures thereof.