Cardiac output measurement with metabolizable analyte containing fluid

• US 5,928,155 A
• Filed: 03/17/1998
• Issued: 07/27/1999
• Est. Priority Date: 01/24/1997
• Status: Expired due to Term

• Current Assignee: Cardiox Corporation
• Original Assignee: Cardiox Corporation
• Inventors: Khalil, Gamal Eddin, Eggers, Philip E., Huntley, Scott P.
• Primary Examiner(s): O'Connor, Cary
• Assistant Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US09/040,167
• Time in Patent Office: 497 Days
• Field of Search: 600/322, 600/341, 600/342, 600/368, 600/478, 600/479, 600/481, 600/508, 600/526, 600/486, 604/20
• US Class Current: 600/526
• CPC Class Codes: A61B 2562/0217 Electrolyte containing
• CPC Class Codes: A61B 5/0215 by means inserted into the body catheters A61M25/00
• CPC Class Codes: A61B 5/0275 using tracers, e.g. dye dilution
• CPC Class Codes: A61B 5/028 by thermo-dilution
• CPC Class Codes: A61B 5/029 Measuring or recording blood output from the heart, e.g. minute volume A61B8/065 takes precedence
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/14542 for measuring blood gases A61B5/14551 takes precedence
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• CPC Class Codes: A61B 5/412 Detecting or monitoring sepsis
• CPC Class Codes: A61B 5/6853 with a balloon
• CPC Class Codes: A61M 2025/0002 with a pressure sensor at the distal end
• CPC Class Codes: A61M 2025/0003 having an additional lumen transmitting fluid pressure to the outside for measurement

Abstract

Cardiac output is measured utilizing a catheter in conjunction with the indicator dilution technique. Non-thermal analyte-containing fluid is used as the injectate. This fluid is biocompatible with and metabolizable within the body of the patient. An analyte concentration sensor is mounted upon the catheter and located downstream within the bloodstream from the port from which the analyte-containing fluid is expressed. Because of the matching of rapid concentration sensor response with an analyte-containing fluid which is metabolizable, the measurement of cardiac output may be carried out as often as about one to three minutes in conjunction with an infusion interval substantially less than the measurement frequency interval. The analyte-containing fluids are selected from a group consisting of ammoniacal fluid, heparin, ethanol, a carbon dioxide releasing fluid, glucose, and anesthesia agent. The system performs in conjunction with a microprocessor-driven controller which automates the measurement procedure and provides a display of cardiac output and various cardiovascular parameters.

Claims

1. Apparatus for determining the cardiac output of the cardiovascular system of the body of a patient, comprising:

a catheter, having an externally disposed proximal end region and an oppositely disposed measurement region position able within the bloodstream of the body;

an indicator channel within said catheter having a fluid input at said proximal end region connected with a controlled source of analyte containing fluid biocompatible with and metabolizable within said body and selected from the group consisting of;

ammoniacal fluid, heparin, ethanol, a carbon dioxide releasing fluid, glucose, anesthesia agent, and excluding oxygen, said indicator dilution channel extending to an infusion outlet at said measurement region from which said analyte containing fluid may be expressed; and

an analyte concentration sensor, responsive to said analyte, having a forward assembly configured for flowing blood contact mounted with said catheter at said measurement region at a location spaced downstream from said infusion outlet when positioned within said bloodstream and having an analyte sensor or concentration sensor output transmissible to said proximal end region corresponding with a concentration level of said analyte within said bloodstream which is correlatable with said cardiac output.

2. The apparatus of claim 1 in which:

said analyte concentration sensor forward assembly comprises an analyte concentration reactor having an output condition in response to the concentration of said analyte; and

a membrane covering said reactor impermeable to blood and permeable to said analyte having an outer surface contactable with said flowing blood; and

said analyte concentration sensor includes;

a transmission assembly for conveying a signal corresponding with said output condition to said catheter proximal end region as said analyte output.

3. The apparatus of claim 2 including:

a sensor channel within said catheter extending from said proximal end region to said analyte concentration sensor forward assembly;

a pH sensor mounted with said catheter at a location for positioning within the bloodstream of said body and wherein;

said analyte-containing fluid is ammoniacal fluid;

said membrane is permeable to gaseous ammonia (NH₃);

said reactor is a gaseous ammonia sensitive dye; and

said transmission assembly is a fiber optic colorimetric measurement assembly which quantitates a change in color of the dye and is mounted within said sensor channel.

4. The apparatus of claim 2 in which:

said analyte containing fluid is an ammonium compound;

said membrane is permeable to ammonium ion (NH₄⁺);

said reactor comprises first and second electrodes immersed within an electrolyte sensitive to said ammonium ion; and

said transmission component comprises a potentiometric assembly coupled with said first and second electrodes.

5. The apparatus of claim 2 in which:

said analyte containing fluid is an ammonium compound;

said membrane is permeable to ammonium ion (NH₄⁺);

said reactor comprises first and second electrodes immersed within an electrolyte sensitive to said ammonium ion; and

said transmission component comprises an amperometric assembly coupled with said first and second electrodes.

6. The apparatus of claim 2 including:

a sensor channel within said catheter extending from said proximal end region to said analyte concentration sensor forward assembly;

said reactor comprises an analyte-sensitive fluorescent material having a fluorescence intensity as said output condition;

said transmission component is a fiber optic assembly for stimulating said reactor and conveying said fluorescence intensity as said output condition.

7. The apparatus of claim 2 including:

a sensor channel within said catheter extending to said analyte concentration sensor forward assembly;

said reactor comprises an analyte-sensitive fluorescent material stimulatable into fluorescence, the rate of quenching of said fluorescence being said output condition; and

said transmission component is a fiber optic assembly for stimulating said reactor and conveying resultant generated light.

8. The apparatus of claim 2 in which said analyte concentration reactor is configured as a Schottky diode array having a conductive polymer responsive to said analyte to effect a forward bias alteration as said analyte sensor output.

9. The apparatus of claim 1 including:

a sensor channel within said catheter extending to said analyte concentration sensor forward assembly;

a pH sensor mounted with said catheter at a location for positioning within the bloodstream of the body;

said analyte is ammonia;

said concentration sensor is a fiber optic assembly within said indicator sensor channel having as said forward assembly a tip adapted for direct light exchange communication with the bloodstream of the body, said fiber optic assembly being extensible to a light source and photoresponsive assembly for measuring the concentration of ammonia gas (NH₃) in the bloodstream.

10. The apparatus of claim 1 including:

a sensor channel within said catheter extending to said analyte concentration sensor forward assembly;

said analyte is ammonium ion (NH₄⁺);

said analyte concentration sensor is an electrode pair immersed in an electrolyte which is ammonium ion sensitive for measuring the concentration of ammonium in the bloodstream.

11. The apparatus of claim 1 in which said analyte concentration sensor comprises:

a fiberoptic assembly extending from said catheter proximal end region to a fiberoptic tip located at and forming a component of said forward assembly;

a membrane forming a component of said forward assembly, impermeable to blood and permeable to said analyte, having an outer surface contactable with said flowing blood and an inner surface spaced from said fiberoptic tip to define an analyte equilibriation cavity; and

including a light transmission and reception assembly optically coupled with said fiberoptic assembly at said proximal end region and actuable to derive said analyte sensor output with respect to analyte at said equilibriation cavity.

12. The apparatus of claim 11, in which said membrane inner surface is light reflecting.

13. The apparatus of claim 1 in which said analyte concentration sensor comprises:

a fiberoptic assembly extending from said catheter proximal region to a fiberoptic tip at said forward assembly, including an outer surface extending inwardly from said fiberoptic tip;

an end plug impervious to blood having an inwardly disposed surface spaced from said fiberoptic tip to define the length of an equilibriation cavity;

a membrane impermeable to blood and permeable to said analyte, having an outer surface contactable with said flowing blood, said membrane extending sealingly about said outer surface and said end plug to define the sides of said equilibration cavity.

14. The apparatus of claim 1 in which said analyte concentration sensor comprises:

a fiberoptic assembly extending from said catheter proximal end region to said forward assembly and having a forward light transmission leg and a return transmission leg spaced from said forward light transmission leg to define a gap situated at said outer assembly; and

a membrane impermeable to blood and permeable to said analyte, having an outer surface contactable with said flowing blood, said membrane sealingly extending about said gap to define an equilibration cavity.

15. The apparatus of claim 1 in which said analyte concentration sensor forward assembly is configured as a Schottky diode array having a conductive polymer responsive to said analyte to effect a forward bias alteration as said analyte output.

16. The apparatus of claim 1 in which said analyte concentration sensor forward assembly comprises an acoustic-wave sensor having an acoustic wave delay line within an oscillator loop to derive said analyte output as a frequency shift.

17. The apparatus of claim 1 including:

a temperature sensor mounted upon said catheter in the vicinity of said analyte concentration sensor and having a temperature value output at said proximal end region corresponding with the temperature of blood within said bloodstream;

an auxiliary port within said catheter in the vicinity of said infusion outlet; and

an auxiliary channel within said catheter extending in fluid transfer communication from said auxiliary port to said proximal end region for delivering fluid through said auxiliary port.

18. A system for determining the cardiac output of the cardiovascular system of the body of a patient, comprising:

a source of analyte-containing fluid biocompatible with and metabolizable within said body and having a predetermined indicator concentration, said analyte being independent of the thermal energy content of said fluid;

fluid flow control apparatus coupled with said source of analyte-containing fluid and controllable to provide a flow of said analyte-containing fluid at a mass flow rate for an infusion interval at a fluid output;

a catheter having an externally disposed proximal end region and an oppositely disposed measurement region positionable within the bloodstream of said body;

an indicator channel within said catheter having a fluid input at said proximal end region connected in fluid transmission relationship with said fluid flow control apparatus fluid output and extending to an infusion outlet at said measurement region from which said analyte-containing fluid may be expressed into the bloodstream of said body;

an analyte concentration sensor, responsive to analyte within said bloodstream to provide a concentration sensor output, having a forward assembly contactable with flowing blood mounted with said catheter at said measurement region at a location spaced from said infusion outlet a dilution measurement distance downstream when positioned within said bloodstream and having a capability for providing said concentration sensor output with a rapidity effective to derive a cardiac output measurement as often as about every one to three minutes and in conjunction with said infusion interval substantially less than said measurement frequency interval;

a controller for controlling said fluid flow control apparatus and said analyte concentration sensor and responsive to each said concentration sensor output for deriving the value of the analyte concentration level within said bloodstream adjacent said forward assembly, responsive to effect control of said analyte concentration sensor to derive a baseline analyte concentration level output, then responsive to effect said flow of said analyte-containing fluid at a predetermined mass flow rate for said infusion interval and for simultaneously controlling said sensor during said infusion interval to derive a subsequent analyte concentration level output, responsive to correlate said baseline analyte concentration level output, said subsequent value for analyte concentration level output, and said predetermined mass flow rate to derive a first output signal representing a value corresponding with cardiac output; and

a display responsive to said first output signal for providing a perceptible output corresponding therewith.

19. The system of claim 18 in which said controller is responsive to a sequence of said baseline analyte concentration level outputs to derive a comparison analyte concentration level in blood corresponding with metabolic homeostasis of said body, and responsive to compare an inputted homeostasis threshold value corresponding with analyte concentration in blood for iatrogenesis with said comparison analyte concentration level in blood to derive a second output signal when said comparison analyte concentration level in blood represents a value greater than said inputted homeostasis threshold value.

20. The system of claim 18 in which said controller controls said fluid flow control apparatus to provide said infusion interval of about two to thirty seconds.

21. The system of claim 18 including:

a pH sensor mounted with said catheter at a location for positioning within the bloodstream of said body and controllable to provide a pH sensor output corresponding with the pH value of blood with which it is in contact;

said controller effects control of said pH sensor to derive said pH sensor output and is responsive to correlate said pH sensor output, said baseline analyte concentration level output, said subsequent analyte concentration level output, and said predetermined mass flow rate to derive said first output signal.

22. The system of claim 21 in which:

said analyte-containing fluid analyte is an ammoniacal fluid;

said analyte concentration sensor output is provided in correspondence with the concentration of ammonia gas (NH₃) in said bloodstream; and

said controller derives a total ammoniacal concentration in blood in correspondence with the expressions;

space="preserve" listing-type="equation">Ca(NH.sub.4.sup.+)=Ca(NH.sub.3)/ 10 exp (pH-pKa)!

space="preserve" listing-type="equation">Ca=Ca(NH.sub.3)+Ca(NH.sub.4.sup.+)

where;

Ca(NH₄⁺) is the concentration of ammonium ions in blood, Ca(NH₃) is the measured concentration of ammonia gas in blood, pH is measured blood pH, pKa is the pH level of solution above which ammoniacal fluid exists only as a gas, and Ca is the total ammoniacal concentration in blood.

23. The system of claim 22 in which said controller derives said first output signal in correspondence with the expression:

##EQU5## where, CO(t_i) is cardiac output measured at time (t_i), K is a constant, m_I is the said mass flow rate of ammoniacal fluid for said infusion interval, ICa is the total ammoniacal concentration of the analyte-containing fluid, Ca(t'"'"'_i) is the total ammoniacal concentration of the analyte-containing fluid in blood based upon said subsequent level analyte concentration level output measured during said infusion interval, and Ca(t_i) is the total ammoniacal concentration in blood based upon said baseline analyte concentration level output.

24. The system of claim 22 in which said analyte concentration sensor is configured to derive said concentration sensor output by optical colorimetry.

25. The system of claim 22 in which said analyte concentration sensor is configured to derive said concentration sensor output as an amperometry signal.

26. The system of claim 22 in which said analyte concentration sensor is configured to derive said concentration output as a potentiometric signal.

27. The system of claim 22 in which said analyte concentration sensor is configured to derive said concentration sensor output employing optical fluorescence.

28. The system of claim 21 in which:

said analyte is carbon dioxide; and

said analyte concentration sensor output is provided in correspondence with the concentration of carbon dioxide in said bloodstream.

29. The system of claim 18 in which said controller is responsive to inputted values representing the height and weight of said body to derive a value for body surface area, and is responsive to a derived value of cardiac output and said value for body surface area to derive an output signal representing a value of cardiac index;

and

said display is responsive to said output signal for displaying said derived value representing cardiac index.

30. The system of claim 29, in which said controller is responsive to an inputted lower threshold limit for cardiac index retained in memory and to said derived value of cardiac index to derive a third output signal when said derived value of cardiac index is below said threshold limit value for cardiac index;

and

said display is responsive to said third output signal for displaying alarm information with respect to said derived value of cardiac index.

31. The system of claim 29, in which said controller is responsive to an inputted upper limit value for cardiac index retained in memory and to said derived value of cardiac index to derive a fourth output signal when said derived value of cardiac index is above said upper limit value for cardiac index;

and

said display is responsive to said fourth output signal for displaying alarm information with respect to said derived value of cardiac index.

32. The system of claim 18 in which:

said controller is responsive to derive a fifth output signal corresponding with the most recently derived analyte concentration level in blood; and

said display is responsive to said fifth output signal for displaying said analyte concentration level in blood.

33. The system of claim 18 in which said source of analyte-containing fluid is selected from the group consisting of ammoniacal fluid, heparin, ethanol, carbon dioxide releasing fluid, glucose, anesthesia agent, and excluding oxygen.

34. The system of claim 18 including:

a pH sensor mounted with said catheter at a location for positioning within the bloodstream of said body and controllable to provide a pH sensor output corresponding with the pH value of the blood;

a blood oxygen saturation sensor mounted with said catheter at a location for positioning within the bloodstream of said body and controllable to provide a mixed venous oxygen saturation output;

a temperature sensor mounted upon said catheter in the vicinity of said analyte concentration sensor and having a temperature value output at said proximal end region corresponding with the temperature of blood within said bloodstream;

said analyte-containing fluid is a carbon dioxide releasing fluid;

said analyte is carbon dioxide; and

said controller effects control of said pH sensor to derive said pH sensor output, effects control of said blood oxygen sensor to derive said mixed venous oxygen saturation output, effects control of said temperature sensor to derive said temperature value output, and is responsive to correlate said pH sensor output, said mixed venous oxygen saturation output, said temperature value output, said baseline analyte concentration level output, an inputted value corresponding with hemoglobin level, and said subsequent analyte concentration level output to derive said first output signal.

35. The system of claim 34 in which:

said concentration sensor output corresponds with the partial pressure of carbon dioxide in plasma (P_plasma CO₂);

said controller derives the concentration of carbon dioxide in plasma (C_plasma CO₂) in accordance with the expression;

space="preserve" listing-type="equation">C.sub.plasma CO.sub.2 =2.226*s*P.sub.plasma CO.sub.2 * 1+10.sup.pH-pK !,

where pH is said pH value of the blood;

said controller derives the value, pK'"'"' in accordance with the expression;

space="preserve" listing-type="equation">pK'"'"'=6.086+ 0.042*(7.4-pH)!+ (38-T)* 0.00472+ 0.00139*(7.4-pH)!!!,

where;

T is said temperature of the blood; and

said controller derives the value, s, in accordance with the following expression;

space="preserve" listing-type="equation">s=0.0307+ 0.00057*(37-T)!+ 0.00002*(37-T).sup.2 !.

36. The system of claim 35 in which:

said controller derives a value for mixed venous carbon dioxide content, CvCO₂, in accordance with the expression;

space="preserve" listing-type="equation">CvCO.sub.2 = C.sub.plasma CO.sub.2 !* 1-0.0289*Hgb/ (3.352-0.456*SvO.sub.2)*(8.142-pH)!,

where Hgb is said hemoglobin level, and SvO₂ is a value corresponding with said mixed venous oxygen saturation output.

37. The system of claim 36 in which:

said controller derives said value for cardiac output, CO, in accordance with the expression;

##EQU6## where (CO(t_i) is cardiac output measured at time (t_i), K is a constant, m CO₂ is said mass flow rate of carbon dioxide within said carbon dioxide releasing fluid, CvCO₂ (t'"'"'_i) is mixed venous carbon dioxide content of blood corresponding with said subsequent analyte concentration level output measured during said infusion interval, and CvCO₂ (t_i) is mixed venous carbon dioxide content of blood corresponding with said baseline analyte concentration level output.

38. The method for determining the cardiac output of the cardiovascular system of the body of a patient, comprising the steps of:

(a) providing a catheter having a proximal end region and extending to a measurement region, an indicator channel within said catheter having a fluid input at said proximal end region and extending to an infusion outlet at said measurement region from which analyte-containing fluid may be expressed, an analyte concentration sensor mounted with said catheter having a forward assembly contactable with flowing blood at said measurement region at a location spaced from said infusion outlet a dilution measurement distance, responsive to the presence of an analyte to provide an output corresponding with the concentration of analyte in blood and having a capability for providing said output within an infusion interval achieving a cardiac output measurement frequency interval of about one to three minutes;

(b) positioning said catheter within the bloodstream of said body, locating said measurement region at the heart region of the patient in a cardiac output measurement orientation wherein said analyte concentration sensor is downstream within said bloodstream from said infusion outlet;

(c) providing a source of analyte-containing fluid biocompatible with and metabolizable within said body and having a predetermined indicator concentration, said analyte being independent of the thermal energy content of said fluid;

(d) deriving a baseline value corresponding with the concentration of said analyte in said bloodstream from said concentration sensor output;

(e) delivering said analyte-containing fluid from said source into said indicator channel input at a predetermined mass flow rate for said infusion interval;

(f) deriving a subsequent value corresponding with the concentration of said analyte in said bloodstream from said concentration sensor concentration output during said infusion interval; and

(g) deriving a value for the cardiac output of the heart of the body by correlating said baseline value, said subsequent value, said indicator concentration, and said predetermined mass flow rate.

39. The method of claim 38 in which said steps (d) through (f) are carried out within a measurement interval frequency of about one to three minutes.

40. The method of claim 38 including the steps of:

(h) selecting a homeostasis threshold value corresponding with an analyte concentration level in blood for iatrogenesis;

(i) determining a baseline concentration of analyte in said bloodstream corresponding with metabolic homeostasis of said body; and

(j) determining whether said concentration of said analyte determined at step (i) exceeds the threshold value selected at step (h).

41. The method of claim 38 in which said analyte-containing fluid is selected from the group consisting of:

ammoniacal fluid, heparin, ethanol, carbon dioxide releasing fluid, glucose, anesthesia agent, and excluding oxygen.

42. The method of claim 38 in which:

said step (a) includes the provision of a pH sensor mounted with said catheter and having a pH sensor output corresponding with the pH value of blood with which it is in contact;

said analyte-containing fluid is an ammoniacal fluid;

said step (d) includes the step;

(d1) obtaining said pH sensor output and deriving the pH value of the blood of said body; and

said step (g) is carried out by correlating the said pH value, said baseline value, said subsequent value, said predetermined indicator concentration and said predetermined mass flow rate.

43. The method of claim 38 in which:

said analyte-containing fluid is an ammoniacal fluid;

said analyte concentration sensor is responsive to ammonia gas;

said step (d) includes the steps;

(d1) obtaining the value of pH of the blood of said body;

(d2) deriving said baseline value in correspondence with the concentration of ammonia gas (NH₃) in said bloodstream;

(d3) deriving from said baseline value the total ammoniacal concentration in blood, in correspondence with the expressions;

space="preserve" listing-type="equation">Ca(NH.sub.4.sup.+)=Ca(NH.sub.3)/ 10 exp (pH-pKa)!

space="preserve" listing-type="equation">Ca=Ca(NH.sub.3)+Ca(NH.sub.4.sup.+)

where Ca(NH₄⁺) is the concentration of ammonium ions in blood, Ca(NH₃) is the measured concentration of ammonia gas in blood, pH is measured blood pH, pKa is the pH level of solution above which ammonia exists as a gas, and Ca is the total ammoniacal concentration in blood.

44. The method of claim 43 in which:

said step (g) derives said value for cardiac output in correspondence with the expression;

##EQU7## where, CO(t_i) is cardiac output measured at time (t_i), K is a constant, m_I is the fluid mass flow rate of ammoniacal fluid, ICa is total ammoniacal concentration of the analyte-containing fluid, Ca(t'"'"'_I) is the total ammoniacal concentration in blood based upon said subsequent value measured during said infusion interval, and Ca(t_i) is the total ammoniacal concentration in blood based upon said baseline value.

45. The method for determining the cardiac output of the cardiovascular system of the body of a patient, comprising the steps of:

(a) providing a catheter having a proximal end region and extending to a measurement region, an indicator channel within said catheter having a fluid input at said proximal end region and extending to an infusion outlet at said measurement region from which analyte-containing fluid may be expressed, an analyte concentration sensor mounted with said catheter having a forward assembly contactable with flowing blood at said measurement region at a location spaced from said infusion outlet a dilution measurement distance, responsive to the presence of an analyte to provide an output corresponding with the concentration of analyte in blood;

(b) positioning said catheter within the bloodstream of said body, locating said measurement region at the heart region of the patient in a cardiac output measurement orientation wherein said analyte concentration sensor is downstream within said bloodstream from said infusion outlet;

(c) providing an analyte-containing fluid selected from the group consisting of;

ammoniacal fluid, heparin, ethanol, carbon dioxide releasing fluid, glucose, anesthesia agent, and excluding oxygen;

(d) deriving a baseline analyte concentration value in said bloodstream from said concentration sensor concentration output;

(e) delivering said analyte-containing fluid from said source into said indicator channel input at a predetermined mass flow rate for an infusion interval;

(f) deriving a subsequent analyte concentration value during said infusion interval from said concentration sensor output; and

(g) deriving a value for the cardiac output of the heart of the body by correlating said baseline analyte concentration value, said subsequent analyte concentration value and said predetermined mass flow rate.

46. The method of claim 45 in which said analyte-containing fluid and said analyte concentration sensor are selected to carry out steps (d) through (f) with said infusion interval achieving a cardiac output measurement frequency of about one measurement each one to three minutes.

47. The method of claim 45 including the steps of:

(h) selecting a homeostasis threshold value corresponding with an analyte concentration level in blood for iatrogenesis;

(i) determining a baseline of analyte in said bloodstream concentration corresponding with metabolic homeostasis of said body; and

(j) determining whether said concentration of analyte determined at step (i) exceeds the threshold value selected at step (h).

48. The method of claim 45 in which:

said analyte-containing fluid is an ammoniacal fluid;

said step (d) includes the steps;

(d1) obtaining the value of pH of the blood of said body;

(d2) deriving said baseline concentration value in correspondence with the concentration of ammonia gas (NH₃) in said bloodstream;

(d3) deriving said baseline analyte concentration value as representing the total ammoniacal concentration in blood in correspondence with the expressions;

space="preserve" listing-type="equation">Ca(NH.sub.4.sup.+)=Ca(NH.sub.3)/ 10 exp (pH-pKa)!

space="preserve" listing-type="equation">Ca=Ca(NH.sub.3)+Ca(NH.sub.4.sup.+)

where Ca(NH₄⁺) is the concentration of ammonium ions in blood, Ca(NH₃) is the measured concentration of ammonia gas in blood, pH is measured blood pH, pKa is the pH level of solution above which ammoniacal fluid exists as a gas, and Ca is the total ammoniacal concentration in blood; and

said step (f) includes the steps of;

(f1) deriving said subsequent analyte concentration value in correspondence with the concentration of ammonia gas (NH₃) in said bloodstream,

(f2) deriving said subsequent analyte concentration value as representing the total ammoniacal concentration in blood in correspondence with the expressions;

space="preserve" listing-type="equation">Ca(NH.sub.4.sup.+)=Ca(NH.sub.3)/ 10 exp (pH-pKa)!

space="preserve" listing-type="equation">Ca=Ca(NH.sub.3)+Ca(NH.sub.4.sup.+)

where Ca(NH₄⁺) is the concentration of ammonium ions in blood, Ca(NH₃) is the measured concentration of ammonia gas in blood, pH is measured blood pH, pKa is the pH level of solution above which ammonia exists as a gas, and Ca is the total ammoniacal concentration in blood.

49. The method of claim 48 in which:

said step (g) derives said value for cardiac output in correspondence with the expression;

##EQU8## where, CO(t_i) is cardiac output measured at time (t_i), K is a constant, m_I is the mass flow rate of ammoniacal fluid, ICa is total ammoniacal concentration of the analyte-containing fluid, Ca(t'"'"'_i) is the total ammoniacal concentration in blood based upon said subsequent value for analyte concentration of ammonia measured during said infusion interval, and Ca(t_i) is the total ammoniacal concentration in blood based upon said baseline analyte concentration.

50. A system for determining the cardiac output of the cardiovascular system of the body of a patient, comprising:

a source of analyte-containing fluid biocompatible with and metabolizable within said body and selected from the group consisting of;

ammoniacal fluid, heparin, ethanol, carbon dioxide releasing fluid, glucose, anesthesia agent, and excluding oxygen;

fluid flow control apparatus coupled with said source of analyte-containing fluid and controllable to provide a flow of said fluid at a mass flow rate for an infusion interval at a fluid output;

a catheter having an externally disposed proximal end region and an oppositely disposed measurement region positionable within the bloodstream of said body;

an indicator channel within said catheter having a fluid input at said proximal end region connected in fluid transfer relationship with said fluid flow control apparatus fluid output and extending to an infusion outlet at said measurement region from which said analyte-containing fluid may be expressed into the bloodstream of said body;

an analyte concentration sensor responsive to said analyte within said bloodstream to provide a concentration sensor output, having a forward assembly contactable with flowing blood mounted with said catheter at said measurement region at a location spaced from said infusion outlet a dilution measurement distance downstream within said bloodstream;

a controller for controlling said fluid flow control apparatus and said analyte concentration sensor, responsive to derive a baseline analyte concentration level in blood, then responsive to effect a flow of said analyte-containing fluid into said catheter fluid input at a predetermined mass flow rate for said infusion interval, responsive to derive a subsequent value for analyte concentration level in blood during said infusion interval, and responsive to correlate said baseline analyte concentration level in blood, said subsequent analyte concentration level in blood and said predetermined mass flow rate to derive a first output signal representing a value corresponding with cardiac output; and

a display responsive to said first output signal for providing a perceptible output corresponding therewith.

51. The system of claim 50 in which said controller controls said fluid flow control apparatus to provide said infusion interval of about two to thirty seconds.

52. The system of claim 50 including:

a pH sensor mounted with said catheter at a location for positioning within the bloodstream of said body and controllable to provide a pH sensor output corresponding with the pH value of blood with which it is in contact;

said controller effects control of said pH sensor to derive said pH sensor output and is responsive to correlate said pH sensor output, said baseline analyte concentration level in blood, said subsequent value for analyte concentration level in blood, and said predetermined mass flow rate to derive said first output signal.

53. The system of claim 52 in which:

said analyte containing fluid is an ammoniacal fluid;

said analyte concentration sensor output is provided in correspondence with the concentration of ammonia gas (NH₃) in said bloodstream; and

said controller derives a total ammoniacal concentration in blood in correspondence with the expressions;

space="preserve" listing-type="equation">Ca(NH.sub.4.sup.+)=Ca(NH.sub.3)/ 10 exp (pH-pKa)!

space="preserve" listing-type="equation">Ca=Ca(NH.sub.3)+Ca(NH.sub.4.sup.+)

where;

Ca(NH₄⁺) is the concentration of ammonium ions in blood, Ca(NH₃) is the measured concentration of ammonia gas in blood, pH is measured blood pH, pKa is the pH level of solution above which ammoniacal fluid exists as a gas, and Ca is the total ammoniacal concentration in blood.

54. The system of claim 53 in which said controller derives said first output signal in correspondence with the expression:

##EQU9## where, CO(t_i) is cardiac output measured at time (t_i), K is a constant, m_I is the said mass flow rate of ammoniacal fluid for said infusion interval, ICa is the total ammoniacal concentration of the analyte-containing fluid, Ca(t'"'"'_i) is the total ammoniacal concentration in blood based upon said subsequent level for analyte concentration measured during said infusion interval, and Ca(t_i) is the total ammoniacal concentration in blood based upon said baseline analyte concentration.

55. The system of claim 53 in which said analyte concentration sensor is configured to derive said concentration sensor output by optical colorimetry.

56. The system of claim 53 in which said analyte concentration sensor is configured to derive said concentration sensor output as an amperometry signal.

57. The system of claim 53 in which said analyte concentration sensor is configured to derive said concentration sensor output as a potentiometry signal.

58. The system of claim 53 in which said analyte concentration sensor is configured to derive said concentration sensor output employing optical fluorescence.

59. The system of claim 50 in which said controller is responsive to inputted values representing the height and weight of said body to derive a value for body surface area, and is responsive to a derived value of cardiac output and said value for body surface area to derive a second output signal representing a value of cardiac index;

and

said display is responsive to said second output signal for displaying said derived value representing cardiac index.

60. The system of claim 59 in which said controller is responsive to an inputted lower threshold limit for cardiac index retained in memory and to said derived value of cardiac index to derive a third output signal when said derived value of cardiac index is below said threshold limit value for cardiac index;

and

said display is responsive to said third output signal for displaying alarm information with respect to said derived value of cardiac index.

61. The system of claim 59 in which said controller is responsive to an inputted upper limit value for cardiac index retained in memory and to said derived value of cardiac index to derive a fourth output signal when said derived value of cardiac index is above said upper limit value for cardiac index;

and

said display is responsive to said fourth output signal for displaying alarm information with respect to said derived value of cardiac index.

62. The system of claim 50 in which:

said controller is responsive to derive a fifth output signal corresponding with instantaneous blood analyte concentration level; and

said display is responsive to said fifth output signal for displaying said blood analyte concentration level.