Measurement of Cardiac Output and Blood Volume by Non-Invasive Detection of Indicator Dilution for Hemodialysis

• US 20080015434A1
• Filed: 05/03/2007
• Published: 01/17/2008
• Est. Priority Date: 05/22/2001
• Status: Active Grant

• Current Assignee: The Alfred E. Mann Institute For Biomedical Engineering At The University Of Southern California (University of Southern California)
• Original Assignee: Alfred E MANN Institute For Biomedical Engineering At The University of Southern California
• Inventors: Rubinstein, Eduardo, Holschneider, Daniel, Maarek, Jean-Michel
• Granted Patent: US 8,337,444 B2
• Time in Patent Office: Days
• US Class Current: 600/431
• CPC Class Codes: A61B 2503/40 Animals
• CPC Class Codes: A61B 5/0275 using tracers, e.g. dye dilution
• CPC Class Codes: A61M 1/16 with membranes
• CPC Class Codes: A61M 1/3609 Physical characteristics of the blood, e.g. haematocrit, urea
• CPC Class Codes: A61M 2230/04 Heartbeat characteristics, e.g. ECG, blood pressure modulation

Abstract

A system and method of non-invasive or minimally invasive evaluating the cardiovascular system parameters to estimate the cardiac output and circulating blood volume of a patient undergoing hemodialysis. Intravascular indicators are stimulated, and emissions patterns detected for computation of cardiac output, cardiac index, blood volume and other indicators of cardiovascular health before and during hemodialysis.

Claims

1. A method of determining non-invasively the cardiac output and the circulating blood volume of a patient undergoing hemodialysis comprising:

a) administering a detectable amount of fluorescent dye to blood of the cardiovascular system of a patient;

b) optically exciting the blood having the administered fluorescent dye with a first wavelength of light and causing the administered fluorescent dye to emit a light having a second wavelength different than the first wavelength;

c) optically detecting the intensity of the emitted light having the second wavelength;

d) estimating the cardiac output and the circulating blood volume of the patient based at least on the detected intensity of the emitted light having the second wavelength;

e) commencing hemodialysis, wherein the hemodialysis comprises removal of blood from the cardiovascular system of the patient;

f) repeating steps a)-d) on the patient during hemodialysis; and

g) adjusting the rate of the blood removal from the patient when the estimated cardiac output and/or the circulating blood volume of the patient at step d) changes significantly during the hemodialysis procedure.

2. The method of claim 1, wherein the fluorescent dye is indocyanine green (ICG).

3. The method of claim 1, wherein the fluorescent dye is administered through inserting a fine catheter at a location selected from the group consisting of:

a peripheral vein, the arterio-venous (AV) fistula, and the arterio-venous (AV) shunt.

4. The method of claim 1, further comprising attaching the probe to an external wall of a transparent tubing of an external dialyzer that is configured to remove the blood from the patient.

5. The method of claim 4, further comprising administering the fluorescent dye through a side port of the dialyzer that is configured to return the dialyzed blood to the patient.

6. The method of claim 1, wherein estimating the cardiac output comprises determining a dilution curve.

7. The method of claim 1, wherein estimating of the circulating blood volume comprises subtracting the removed blood volume in the dialyzer'"'"'s compartment from the total circulating blood volume.

8. The method of claim 2, wherein the optical detection further comprises detecting from the removed blood an emitted intensity of light having the first wavelength.

9. The method of claim 8, wherein the detecting of the light having the first wavelength comprises detecting reflected and/or transmitted light that is emitted by the blood.

10. The method of claim 2, wherein the light having the second wavelength comprises back-fluorescence and/or forward-fluorescence that is emitted from the fluorescent dye.

11. The method of claim 2, wherein the optical detecting further comprises detecting a plurality of light intensities having different wavelengths.

12. The method of claim 11, further comprising a pre-calibrating the probe prior to the administration of the ICG.

13. The method of claim 12, wherein the calibration is a non-invasive and in-vitro process.

14. The method of claim 11, wherein the estimating of cardiac output comprises determining the ICG concentration.

15. The method of claim 14, wherein the ICG concentration is determined based on detected transmitted light intensity and the detected back-fluorescence having a relationship comprising:

C_ICG=A.T^α

.B_Fluo

where C_ICG is the blood ICG concentration, B_Fluo represents the back-fluorescence intensity having the second wavelength, T is the transmitted light intensity having the first wavelength, and parameters A and α

are predetermined constants.

16. The method of claim 14, wherein the ICG concentration is determined based on detected transmitted light intensity and the detected forward-fluorescence having a relationship comprising:

C_ICG=B.T^β

.F_Fluo

where C_ICG is the blood ICG concentration, F_Fluo represents the forward-fluorescence intensity having the second wavelength, T being the transmitted light intensity having the first wavelength, and parameters B and β

are predetermined constants.

17. The method of claim 14, wherein the ICG concentration is determined based on the detected reflected light intensity and the back-fluorescence having a relationship comprising:

C_ICG=K.R^γ

.B_Fluo

where C_ICG is the blood ICG concentration, R is the reflected light intensity having the first wavelength and B_Fluo being the fluorescence intensity having the second wavelength, and the exponent γ and

parameter K are predetermined constants.

18. The method of claim 14, wherein the ICG concentration is determined based on detected reflected light intensity and the detected forward-fluorescence having a relationship comprising:

C_ICG=K.R^γ

.F_Fluo

where C_ICG is the blood ICG concentration, F_Fluo represents the forward-fluorescence intensity having the second wavelength, R being the reflected light intensity having the first wavelength, and the exponent γ and

parameter K are the predetermined constants.

19. The method of claim 14, wherein the ICG concentration is determined based on the detected reflected light, back-fluorescence and the transmitted light having a combination of relationships comprising:

C_ICG=B.T^β

.B_Fluo and C_ICG=K.R^γ

.B_Fluo

where C_ICG is the blood ICG concentration, B_Fluo represents the back-fluorescence intensity having the second wavelength, T is the transmitted light intensity having the first wavelength, R is the reflected light intensity having the first wavelength, and parameters A, K, α

, γ

are predetemined constants.

20. The method of claim 14, wherein the ICG concentration is determined based on the detected reflected light, forward-fluorescence and the transmitted light as follows:

C_ICG=B.T^β

.F_Fluo and C_ICG=K.R^γ

.F_Fluo

where C_ICG is the blood ICG concentration, F_Fluo represents the forward-fluorescence intensity having the second, T is the transmitted light intensity, R is the reflected light intensity, and parameters B, K, β

, γ

are predetermined constants.

21. A system for determining non-invasively the cardiac output and the circulating blood volume of a patient undergoing hemodialysis comprising:

a) a dialyzer configured to perform hemodialysis on the patient, wherein the hemodialysis comprises blood removal from the cardiovascular system of the patient;

b) a probe assembly comprising;

i) an optical illumination source configured to illuminate the removed blood having an administered fluorescent dye with a first wavelength of light, wherein the illumination and causes the fluorescent dye to emit light of a second wavelength; and

ii) at least one optical detector configured to detect the intensity of light, having the second wavelength, that is emitted from the illuminated fluorescent dye, and configured to send a corresponding electronic signal;

c) a processor configured to receive the sent electronic signal before and during the hemodialysis procedure, and to estimate the cardiac output and the circulating blood volume of the patient based on the sent electronic signal; and

d) a monitoring system configured to monitor the estimated cardiac output and/or the circulating blood volume during hemodialysis, and to adjust the rate of the blood removal from the patient when the estimated cardiac output and/or the circulating blood volume changes significantly.

22. The system of claim 21, wherein the administered fluorescent dye is indocyanine green (ICG).

23. The system of claim 21, wherein the fluorescent dye is administered through inserting a fine catheter at any of peripheral vein, the arterio-venous (AV) fistula or the arterio-venous (AV) shunt.

24. The system of claim 21, wherein the dialyzer further comprises a transparent tubing configured to remove blood from the patient to the dialyzer, and wherein the probe is configured to be attached to the external wall of the tubing.

25. The system of claim 21, wherein the probe further comprises a second optical detector configured to detect a light intensity having the first wavelength.

26. The system of claim 25, wherein the second optical detector is configured to detect one of the reflected or transmitted light that is emitted from the removed blood.

27. The system of claim 22, wherein the optical detector is configured to detect one of the back-fluorescence or forward-fluorescence that is emitted by the fluorescent dye.

28. The system of claim 22, wherein the probe further comprises a plurality of optical detectors that are configured to detect plurality of light intensities having the same or different wavelengths.

29. The system of claim 22, wherein the probe is pre-calibrated.

30. The system of claim 29, wherein the probe is calibrated non-invasively and in-vitro.

31. The system of claim 28, wherein the processor is further configured to determine the ICG concentration.

32. The system of claim 31, wherein the processor is configured to determine the ICG concentration based on a relationship:

C_ICG=A.T^α

.B_Fluo

where C_ICG is the blood ICG concentration, B_Fluo represents the back-fluorescence intensity having the second wavelength, T is the transmitted light intensity having the first wavelength, and parameters A and α

are predetermined constants.

33. The system of claim 31, wherein the processor is configured to determine the ICG concentration based on a relationship:

C_ICG=B.T^β

.F_Fluo

where C_ICG is the blood ICG concentration, F_Fluo represents the forward-fluorescence intensity having the second wavelength, T is the transmitted light intensity having the first wavelength and parameters B and β

are predetermined constants.

34. The system of claim 31, wherein the processor is configured to determine the ICG concentration based on a relationship:

C_ICG=K.R^γ

.F_Fluo

where C_ICG is the blood ICG concentration, B_Fluo is the fluorescence intensity having the second wavelength, R is the reflected light intensity having the first wavelength and the exponent γ and

parameter K being predetermined constants.

35. The system of claim 31, wherein the processor is configured to determine the ICG concentration based on a relationship:

C_ICG=K.R^γ

.F_Fluo

where C_ICG is the blood ICG concentration, F_Fluo represents the forward-fluorescence intensity having the second wavelength, R is the reflected light intensity having the first wavelength, and parameters K and γ

are predetermined constants.

36. The system of claim 28, wherein the processor is configured to determine the ICG concentration based on combined relationships:

C_ICG=A.T^α

.B_Fluo and C_ICG=K.R^γ

.B_Fluo

where C_ICG is the blood ICG concentration, B_Fluo represents the back-fluorescence intensity having the second wavelength, T and R being the transmitted and reflected lights, respectively, having the first wavelength and parameters A, K, α and

γ

are predetermined constants.

37. The system of claim 31, wherein the processor is configured to determine the ICG concentration based on combined relationships:

C_ICG=B.T^β

.F_Fluo and C_ICG=K.R^γ

.F_Fluo

where C_ICG is the blood ICG concentration, F_Fluo represents the forward-fluorescence intensity having the second wavelength, T and R are the transmitted and the reflected light intensities having a wavelength different than the second wavelength and the parameters B, K, β and

γ

are predetermined constants.

38. The system of claim 21, wherein the dialyzer further comprises a side port configured to return the dialyzed blood to the patient, and wherein the fluorescent dye is administered through the side port into the cardiovascular system of the patient.

39. The system of claim 21, wherein the processor further configured to estimate the cardiac output through a dilution curve.

40. The system of claim 21, wherein the processor further configured to estimate the circulating blood volume through subtracting the removed blood volume in the dialyzer'"'"'s compartment from the total circulating blood volume of the patient.

41. A probe for detecting a plurality of light intensities of different wavelengths while removing blood from a subject'"'"'s cardiovascular system comprising:

a) at least one optical fiber configured to illuminate the blood having an administered fluorescent dye while the blood is being removed from a subject, wherein the blood is illuminated with light having a first wavelength;

b) at least one optical fiber configured to detect the intensity of light having a second wavelength that is reflected from the illuminated fluorescent dye within the blood;

c) at least one optical fiber configured to detect the intensity of light having the first wavelength that is reflected from the illuminated blood;

d) at least one optical fiber configured to detect the intensity of light having the first wavelength that is transmitted through the illuminated blood; and

e) at least one optical fiber configured to detect the intensity of light having the second wavelength that is transmitted through the illuminated fluorescent dye within the blood.

42. The probe of claim 41, wherein the probe is configured to be attached to a transparent carrier that removes the blood from the subject.

43. The probe of claim 42, wherein the optical fiber in b) is configured to detect back-fluorescence intensity.

44. The probe of claim 42, wherein the optical fiber in e) is configured to detect forward-fluorescence intensity.

45. The probe of claim 41, wherein any one of the optical fibers in b)-e) is a different fiber from the others.

46. The probe of claim 45, wherein each of the optical fibers b) to e) is configured to detect one designated light intensity that is different from the other detected light intensities.

47. The probe of claim 41, wherein the optical fibers b) to e) are configured to simultaneously detect all or any combination of the light intensities.

48. The probe of claim 41, wherein the optical fibers b) to e) further comprise a plurality of optical fibers that are configured to detect their designated light intensities.