Claims for Patent: 10,028,995

Summary for Patent: 10,028,995

Title:	Angiotensin II alone or in combination for the treatment of hypotension
Abstract:	The present invention relates, inter alia, to a method comprising administering to a subject having high output shock and undergoing treatment with a catecholamine at a dose equivalent to at least about 0.2 mcg/kg/min of norepinephrine a dose of angiotensin II which is effective to raise the blood pressure of the subject to a mean arterial pressure (MAP) of about 65 mm or above, and which is effective to reduce the dose of the catecholamine required to maintain a MAP of about 65 mm to the equivalent of about 0.05-0.2 mcg/kg/min norepinephrine or less, or to the equivalent of about 0.05 mcg/kg/min norepinephrine or less.
Inventor(s):	Chawla; Lakhmir (McLean, VA)
Assignee:	The George Washington University a Congressionally Chartered Not-for-Profit Corporation (Washington, DC)
Application Number:	14/941,301
Patent Claims:	1. A method for maintaining a mean arterial pressure (MAP) of 65 mm Hg or above in a patient suffering from hypotension and undergoing treatment with vasopressin, comprising: administering angiotensin II to the patient; and reducing the rate at Which vasopressin is administered, while maintaining the MAP of the patient at about 65 mm Hg or above. 2. The method of claim 1, wherein vasopressin is administered at a dose of about 0.01 U/min to about 0.08 U/min. 3. The method of claim 2, wherein vasopressin is administered at a dose of about 0.01 U/min to about 0.04 U/min. 4. The method of claim 2, wherein vasopressin is administered at a dose of 0.02 U/min to 0.08 U/min. 5. The method of claim 1, wherein vasopressin is administered at a dose of at least 0.08 U/min. 6. The method of claim 1, wherein reducing the rate at which vasopressin is administered comprises reducing the rate by at least about 20%. 7. The method of claim 1, further comprising administering a catecholamine to the subject. 8. The method of claim 7, wherein the catecholamine is dopamine, norepinephrine, epinephrine, phenylephrine, or ephedrine. 9. The method of claim 7, wherein the catecholamine is administered at a dose equivalent to about 0.01 mg/kg/min to about 0.1 mcg/kg/min norepinephrine. 10. The method of claim 9, wherein: the catecholamine is norepinephrine; the catecholamine is epinephrine and the dose equivalent to 0.1 mcg/kg/min of norepinephrine is 0.1 mcg/kg/min epinephrine; the catecholamine is dopamine and the dose equivalent to 0.1 mcg/kg/min of norepinephrine is 15 mcg/kg/min dopamine; or the catecholamine is phenylephrine and the dose equivalent to 0.1 mcg/kg/min of norepinephrine is 1.0 mcg/kg/min phenylephrine. 11. The method of claim 1, wherein the method comprises administering angiotensin II at an initial rate of about 1 ng/kg/min to about 20 ng/kg/min. 12. The method of claim 11, wherein the angiotensin II is administered at an initial rate of about 1 ng/kg/min to about 10 ng/kg/min. 13. The method of claim 11, wherein the angiotensin II is administered at an initial rate of about 1 ng/kg/min to about 5 ng/kg/min. 14. The method of claim 1, wherein the angiotensin II comprises the amino acid sequence set forth in SEQ ID NO:1; SEQ ID NO:2; SEQ ID NO:3; SEQ ID NO:4; SEQ ID NO:5; SEQ ID NO:6; SEQ ID NO:7; or SEQ ID NO:8. 15. The method of claim 14, wherein the angiotensin II comprises the amino acid sequence set forth in SEQ ID NO:1. 16. The method of claim 15, wherein the angiotensin II consists of the amino acid sequence set forth in SEQ ID NO:1. 17. The method of claim 1, further comprising reducing the rate at which the angiotensin II is administered, while maintaining the MAP of the patient at about 65 mm Hg or above. 18. The method of claim 17, wherein reducing the rate at which angiotensin II is administered comprises reducing the rate to about 5-10 ng/kg/min. 19. The method of claim 17, wherein reducing the rate at which angiotensin II is administered comprises reducing the rate to about 1.25-5 ng/kg/min. 20. The method of claim 17, wherein reducing the rate at which angiotensin II is administered comprises reducing the rate to about 0.25-1.25 ng/kg/min. 21. The method of claim 1, wherein the patient has shock, septic shock, shock from cardiac arrest, cardiogenic shock, high output shock, acute kidney injury, hepatorenal syndrome, variceal bleeding, liver cirrhosis, or portal hypertension. 22. The method of claim 1, wherein the patient is catecholamine-resistant. 23. A method for maintaining a mean arterial pressure (MAP) of 65 mm Hg or above in a patient suffering from hypotension and undergoing treatment with a vasopressin analogue, comprising: administering angiotensin II to the patient; and reducing the rate at which the vasopressin analogue is administered, while maintaining the MAP of the patient at about 65 mm Hg or above. 24. The method of claim 23, wherein the vasopressin analogue is vasopressin, terlipressin, argipressin, desmopressin, felypressin, lypressin, or ornipressin. 25. The method of claim 23, wherein the angiotensin II comprises the amino acid sequence set forth in SEQ ID NO:1; SEQ ID NO:2; SEQ ID NO:3; SEQ ID NO:4; SEQ ID NO:5; SEQ ID NO:6; SEQ ID NO:7; or SEQ ID NO:8. 26. The method of claim 25, wherein the angiotensin II comprises the amino acid sequence set forth in SEQ ID NO:1. 27. The method of claim 26, wherein the angiotensin II consists of the amino acid sequence set forth in SEQ ID NO:1. 28. The method of claim 23, further comprising reducing the rate at which the angiotensin II is administered, while maintaining the MAP of the patient at about 65 mm Hg or above. 29. The method of claim 28, wherein reducing the rate at which the angiotensin II is administered comprises reducing the rate to about 5-10 ng/kg/min. 30. The method of claim 28, wherein reducing the rate at which the angiotensin II is administered comprises reducing the rate to about 1.25-5 ng/kg/min. 31. The method of claim 28, wherein reducing the rate at which the angiotensin II is administered comprises reducing the rate to about 0.25-1.25 ng/kg/min. 32. The method of claim 23, wherein the patient has shock, septic shock, shock from cardiac arrest, cardiogenic shock, high output shock, acute kidney injury, hepatorenal syndrome, variceal bleeding, liver cirrhosis, or portal hypertension. 33. The method of claim 23, wherein the patient is catecholamine-resistant. 34. The method of claim 23, wherein the patient is undergoing treatment with a vasopressin and a catecholamine. 35. The method of claim 34, wherein the catecholamine is dopamine, norepinephrine, epinephrine, phenylephrine, or ephedrine. 36. The method of claim 34, wherein the catecholamine is administered at a dose equivalent to about 0.01 mg/kg/min to about 0.1 mcg/kg/min norepinephrine. 37. The method of claim 35, wherein: the catecholamine is norepinephrine; the catecholamine is epinephrine and the dose equivalent to 0.1 mcg/kg/min of norepinephrine is 0.1 mcg/kg/min epinephrine; the catecholamine is dopamine and the dose equivalent to 0.1 mcg/kg/min of norepinephrine is 15 mcg/kg/min dopamine; or the catecholamine is phenylephrine and the dose equivalent to 0.1 mcg/kg/min of norepinephrine is 1.0 mcg/kg/min phenylephrine. 38. The method of claim 23, wherein the method comprises administering angiotensin II at an initial rate of about 1 ng/kg/min to about 20 ng/kg/min. 39. The method of claim 38, wherein the angiotensin II is administered at an initial rate of about 1 ng/kg/min to about 10 ng/kg/min. 40. The method of claim 38, wherein the angiotensin II is administered at an initial rate of about 1 ng/kg/min to about 5 ng/kg/min.