Method and system for non-invasive measurement of cardiac parameters

Abstract

A method and system are presented for use in assessment of at least one cardiac parameter of an individual. An electrodes arrangement is applied to an individual's body, for applying an electrical field to the body and providing an electrical output indicative of a systolic impedance change and of a velocity of said change during a cardiac cycle. Also provided is additional data indicative of at least of the following conditions of the individual: a value of total peripheral resistance (TPR), a value of cardiac index (CI), and existence of the AHF condition. Data corresponding to these condition is analyzed to determine whether the TPR satisfies a first predetermined condition and/or the CI satisfies a predetermined second condition and/or whether the acute heart failure (AHF) condition is identified, to thereby use the data indicative of the measured electrical output and selectively calculate said at least one cardiac parameter based on either the systolic impedance change data or on said data of the velocity of the impedance change.

Claims

1. An impedance measurement system for assessment of at least one cardiac parameter of an individual, the impedance measurement system comprising: a measurement unit comprising an electrodes arrangement comprising a first and second electrode sets, the first electrode set being configured and operable to attach to one arm at a first lateral side of the individual's body and the second electrode set being configured and operable to attach to one leg at a second lateral side of the individual's body, said electrodes arrangement being configured and operable to apply an electrical field to the body through one of the first and second electrode sets and to obtain an electrical output through the other of the first and second electrode sets, said electrical output comprising measured data indicative of both systolic impedance change, ΔR, and velocity of a systolic impedance change, δR/δt, of the individual during a cardiac cycle; and a control unit comprising: a data input utility configured and operable for receiving input data indicative of at least one condition of the individual, said at least one condition being indicative of whether the individual is sustained by an acute heart failure (AHF), and for receiving said measured data; a processor programmed for analyzing said input data indicative of said at least one condition of the individual, and upon identifying that said input data is indicative of that the individual is sustained by AHF, selecting the data of the velocity of systolic impedance change for calculating the at least one cardiac parameter of the individual, and upon identifying that said input data is indicative of that the individual is not sustained by AHF, either selecting the data of systolic impedance change for calculating the at least one cardiac parameter, or analyzing additional input data indicative of at least one other predetermined condition of the individual in order to determine whether to use the systolic impedance change data or the velocity of systolic impedance change data, said at least one other condition comprising value of at least one of a total peripheral resistance (TPR) and a cardiac index (CI); and a data output utility configured and operable for generating an output indicative of the calculation result.

2. The computer system of claim 1, wherein said at least one cardiac parameter is selected from the following: stroke volume, cardiac output, cardiac index, stroke index, heart rate.

3. The computer system of claim 1, wherein said processor utilizes first measured data of the systolic impedance change and second measured data indicative of at least an individual's blood pressure; in order to determine the individual's TPR.

4. The computer system of claim 1, wherein said CI is determined as CI=CO/BSA, where BSA is the individual's body surface area, and CO is the individual's cardiac output determined from the measured data.

5. The computer system of claim 1, wherein said at least one other predetermined condition is satisfied when the measured TPR value is higher than a value ranging from 1800 dynes/sec.sup.−5 to 1900 dynes/sec.sup.−5.

6. The computer system of claim 1, wherein said at least one other predetermined condition is satisfied when the cardiac index is above 2.5.

7. The computer system of claim 1, wherein the calculation of said at least one cardiac parameter based solely on the systolic impedance change data is performed using the Frinerman formula: $\mathrm{SV}=\frac{{\mathrm{Hct}}_{\mathrm{corr}.}}{K\left(\mathrm{sex},\mathrm{age}\right)}.Math.\frac{\Delta R}{R}.Math.\frac{H_{\mathrm{corr}}^2}{R}.Math.\frac{\alpha +\beta }{\beta }.Math.K_{\mathrm{el}}.Math.K_w.Math.\mathrm{IB}$ wherein: Hct.sub.corr is the correcting factor depending from Hematocrit; Hct is the Hematocrit; K.sub.sex, age is the coefficient of the individual's body depending on the sex and age of the individual; R is the basic resistance of the individual's body during one cardiocycle; H.sup.2.sub.corr is the corrected height of the patient; K.sub.el is the coefficient of electrolytic ions in the individual's blood; K.sub.w is the weight coefficient for the corresponding sex and age of the individual; and IB is the index balance.

8. The computer system of claim 1, wherein the calculation of said at least one cardiac parameter based solely on the systolic impedance change data is performed using a formula $\mathrm{SV}=\frac{\Delta R.Math.\rho .Math.L^2.Math.\left(\alpha +\beta \right).Math.\mathrm{KW}.Math.\mathrm{HF}}{R.Math.R_i.Math.\beta }$ wherein SV is the cardiac stroke volume (ml), ΔR is the blood resistance change (ohm) during the cardiac cycle, R is the basal resistance (ohm), R.sub.i is the corrected basal resistance (ohm), ρ is the specific resistivity of blood (ohm/cm), L is the individual's height (cm), KW is the corrected factor for the body weight, HF is the hydration factor related to the body's water composition, (α+β)/β is the ratio between the systolic and diastolic time intervals α and β and the diastolic time β for the ΔR waveform.

9. The computer system of claim 1, wherein the calculation of said at least one cardiac parameter based solely on the systolic impedance change data is performed using a formula: $\mathrm{SV}=\frac{\Delta R.Math.k_{\mathrm{HR}}.Math.\left(\alpha +\beta \right)}{\beta }.Math.\rho .Math.\frac{L^2}{R.Math.R_i}.Math.\mathrm{KW}.Math.\mathrm{HF}$ wherein SV is the cardiac stroke volume (ml), ΔR is the blood resistance change (ohm) during the cardiac cycle, R is the basal resistance (ohm), R.sub.i is the corrected basal resistance (ohm), ρ is the specific resistivity of blood (ohm/cm), L is the individual's height (cm), KW is the corrected factor for the body weight, HF is the hydration factor related to the body water composition, (α+β)/β is the ratio between the systolic and diastolic time intervals α and β and the diastolic time β for the AR waveform, and k.sub.HR is the heart rate coefficient for correction.

10. The computer system of claim 1, wherein the calculation of said at least one cardiac parameter based solely on said data of the velocity of the impedance change is performed using a formula: $\mathrm{SV}=k_{\mathrm{dr}}.Math.\frac{dR}{dt}.Math.T.Math.\rho .Math.{\left(\frac{L}{R}\right)}^2$ wherein SV is the cardiac stroke volume (ml), dR/dt is the peak of the first derivative of the blood resistance change during the cardiac cycle (ohm/sec), R is the basal resistance (ohm), T is the cardiac ejection time (sec), L is the length between voltage pick-up electrodes, and k.sub.dr is a calibration factor.

11. The computer system of claim 1, wherein the calculation of said at least one cardiac parameter based solely on said data of the velocity of the impedance change is performed using a formula: $\mathrm{SV}=k_{\mathrm{dr}}.Math.\frac{dR}{dt}.Math.T.Math.\rho .Math.\frac{L^2}{R.Math.R_i}.Math.\mathrm{KW}.Math.\mathrm{HF}$ wherein SV is the cardiac stroke volume (ml), dR/dt is the peak of the first derivative of the blood resistance change during the cardiac cycle (ohm/sec), R is the basal resistance (ohm), R.sub.i is the corrected basal resistance (ohm), ρ is the specific resistivity of blood (ohm/cm), T is the cardiac ejection time (sec), L is the length between voltage pick-up electrodes, KW is the corrected factor for the body weight, HF is the hydration factor related to the body water composition, and k.sub.dr is a calibration factor.

12. The computer system of claim 1, wherein said calculation of said at least one cardiac parameter based on either the systolic impedance change data or on said data of the velocity of the impedance change is performed by a two-part equation $\mathrm{SV}=\left[\frac{\Delta R.Math.k_{\mathrm{HR}}.Math.\left(\alpha +\beta \right)}{\beta }+k_{\mathrm{dr}}.Math.\frac{dR}{dt}.Math.T\right].Math.\rho .Math.\frac{L^2}{R.Math.R_i}.Math.\mathrm{KW}.Math.k_{\mathrm{HF}}$ wherein SV is the cardiac stroke volume (ml), ΔR is the blood systolic impedance change (ohm) during the cardiac cycle, dR/dt is the peak of the first derivative of the blood resistance change during the cardiac cycle (ohm/sec), R is measured basal resistance (ohm), R.sub.i is the corrected basal resistance (ohm), ρ is the specific resistivity of blood (ohm/cm), L is the individual's height (cm), KW is the corrected factor for the body weight, HF is the hydration factor related to the body water composition, (α+β)/β is the ratio between the systolic and diastolic time intervals α and β and the diastolic time β for the ΔR waveform, and k.sub.dr is a calibration factor, and k.sub.HR is the heart rate coefficient for correction, while the coefficients k.sub.HR and k.sub.dr are set to 0 and 1 respectively when said at least one of the first and second conditions is satisfied and set to 1 and 0 where said at least one condition is not satisfied.

13. The computer system of claim 12, wherein the processor is adapted to determine the TPR data by processing the first measured data of the systolic impedance change and second measured data indicative of at least an individual's blood pressure.

14. The computer system of claim 13, wherein the CI is determined by: CI=CO/BSA, where BSA is the individual's body surface area, and where CO is the individual's cardiac output determined from the measured data.

15. The computer system of claim 12, wherein said at least one other predetermined condition is satisfied when the measured TPR value is about 30% higher than a top limit of a normal range.

16. The computer system of claim 15, wherein said at least one other predetermined condition is satisfied when the measured TPR value exceeds a value in a range from about 1800 (dynes/cm.sup.−5) to about 1900 (dynes/sec.sup.−5).

17. The computer system of claim 12, wherein said at least one other predetermined condition is satisfied when the cardiac index is above 2.5.

18. The computer system of claim 1, wherein said data input utility is configured for communication with a measurement unit for receiving said measured data.

19. The computer system of claim 1, wherein the calculation of the at least one cardiac parameter takes into account the patient's heart rate.

20. The measurement system of claim 1, wherein each of said electrode sets comprises one electrode or a pair of electrodes, and wherein said electrode arrangement comprises an additional electrode for use in an ECG measurement.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) In order to understand the invention and to see how the same may be carried out in practice, some preferred embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which:

(2) FIGS. 1A and 1B are schematic illustrations of the main constructional parts and operational principles of a measuring system according to one example of the invention utilizing the tetrapolar mode;

(3) FIGS. 2A and 2B are schematic illustrations of the main construction parts and operational principles of a measuring system according to another example of the invention utilizing the bipolar mode;

(4) FIGS. 3A and 3B are block diagrams showing more specifically two examples, respectively, of the configuration of the measuring system according to the invention; and

(5) FIGS. 4A to 4C show three examples, respectively, of a method according to the invention for determining the patient's stroke volume.

DESCRIPTION OF SOME EXEMPLARY EMBODIMENTS

(6) Referring to FIG. 1A, there is exemplified an impedance measurement system 10A of the present invention for use in assessment of at least one cardiac parameter of an individual (such as stroke volume, heart rate, cardiac output, cardiac index, etc.). Impedance measurement system 10A includes a measurement system 12 and a control system 18.

(7) Measurement system 12 includes an electrodes' arrangement 14 for attaching to individual's 5 extremities, and an electrical integral bioimpedance measuring unit 15A. In the present example, system 10A is configured for the tetrapolar mode of operation. To this end, electrodes arrangement 14 is configured to define two pairs of electrodes, which in the present example is implemented by using four electrodes, E.sub.1-E.sub.1′ and E.sub.2-E.sub.2′ for applying a weak electrical current (e.g. about 0.5-2 mA, e.g. 1.4 mA) through the body and measuring an electrical output of the body. The electrical output is indicative of a systolic impedance change (volumetric change) and of a velocity of said change during a cardiac cycle. The first electrode unit E.sub.1-E.sub.1′ is applied to the patient's arm and the second electrode unit E.sub.2-E.sub.2′ is applied to the patient's leg. The electrodes are connected to electrical integral bioimpedance measuring unit 15A which is connectable (via wires or via wireless signal transmission) to control system 18.

(8) FIG. 1B shows an electrical scheme defined by the above configuration of the electrodes' arrangement. As shown, locations 3-3a and 4-4a of the two pairs of electrodes E.sub.1-E.sub.1′ and E.sub.2-E.sub.2′, respectively, define two impedance regions of the skin between the electrodes of each pair, Z.sub.skin, and the body impedance regions Z.sub.1, Z.sub.2, Z.sub.3 and Z.sub.4.

(9) FIGS. 2A and 2B illustrate, respectively, an example of a measurement system 10B configured for the bipolar mode of operation utilizing an electrical integral bioimpedance measuring unit 15B, and an electrical scheme of such a system. To facilitate understanding, the same reference numerals are used for identifying components that are common in all the examples of the invention.

(10) In both examples of FIGS. 1A-1B and 2A-2B, control system 18 is typically a computer system including inter alia data input and output utilities (not shown), memory utility 18A for storing reference data and a model data used for calculations, data processing and analyzing utility 18B, display 18C.

(11) The control system is preprogrammed to analyze the detected signal (electrical output), according to the method of the present invention. The control system is adapted to calculate the TPR utilizing the patient's blood pressure data BP and the measured systolic impedance change from the electrical output. To this end, the control system calculates the cardiac output as a product of the measured stroke volume (calculated from the electrical output) and the heart rate. The latter can be obtained from the ECG measurement or from the impedance wave. The control system then operates to analyze the TPR data, for determining whether the TPR satisfies a first predetermined condition, to thereby apply a predetermined model configured to selectively calculate said at least one cardiac parameter based on either the volumetric change data or on the velocimetric impedance data. Output data indicative of the calculation results is then generated and presented (e.g. displayed).

(12) The selective determination of the required parameter based on either the volumetric change data or on the velocimetric impedance data is associated with the following. The calculation of the left ventricular (LV) stroke volume (SV) by means of impedance cardiography (ICG) is based on two different physico-physiological principles, each of which can be independently used for measuring impedance changes of different origin which are incurred by the arterial pulsations.

(13) The first physico-physiological principle is based on the volumetric changes. This principle uses an algorithm based on the electrical signal of the systolic impedance variation (SIV) generated by the increase of the intra-arterial pulse volume. The basic variable in the respective formula of this algorithm is ΔR/R, multiplied by outflow decay (α+η)/β, where R is the value of basal resistance of the body (ohm), ΔR is the value of the SIV (Ohm), α and β are the systolic and diastolic time intervals, (α+β) being the time of a cardiac cycle, β being the descending part of the ΔR curve.

(14) For this purpose, the following calculation modes can be used:

(15) (1) Generally, the known Frinerman formula can be used (see U.S. Pat. No. 5,469,859 assigned to the assignee of the present application):

(16) $\begin{array}{cc}SV=\frac{{\mathrm{Hct}}_{\mathrm{corr}}}{K\left(\mathrm{sex},\mathrm{age}\right)}.Math.\frac{\Delta R}{R}.Math.\frac{H_{\mathrm{corr}}^2}{R}.Math.\frac{\alpha +\beta }{\beta }.Math.K_{el}.Math.K_w.Math.\mathrm{IB}& \left(1\right)\end{array}$
wherein:

(17) Hct.sub.corr is the correcting factor depending from Hematocrit, being (145+0.35(Hct−40);

(18) Hct is the Hematocrit level/value, obtained from the blood analysis of the individual;

(19) K.sub.sex, age is the coefficient of the individual's body depending on the sex and age of the individual, and is determined as follows: (527.3−(3.1.Math.(Actual Age-20))) for men younger than 20 years; 527.3 for men from 20 to 40 years; (527.3+(3.1.Math.(Actual Age-40))) for men older than 40 years; (587.6−(2.9.Math.(Actual Age-18))) for women younger than 18 years; 587.6 for women from 18 to 50 years; and (587.6+((2.9.Math.(Actual Age-50))), for women older than 50 years;

(20) H.sup.2 corr is the corrected height of the patient, given by:

(21) $H_{\mathrm{corr}}=\left(H_{\mathrm{real}}+2\right)\mathrm{if}\frac{\mathrm{legs}\mathrm{length}}{\mathrm{body}\mathrm{length}}=0.66\pm 0.04$$\mathrm{or}$$H_{\mathrm{corr}}=\left(H_{\mathrm{real}}-2\right)\mathrm{if}\frac{\mathrm{legs}\mathrm{length}}{\mathrm{body}\mathrm{length}}=0.54\pm 0.04$$\mathrm{or}$$H_{\mathrm{corr}}=\left(H_{\mathrm{real}}\right)\mathrm{if}0.62\ge \frac{\mathrm{legs}\mathrm{length}}{\mathrm{body}\mathrm{length}}\ge 0.58$

(22) K.sub.el is the coefficient of electrolytic ions in the individual's blood, calculated based on the blood analysis and being given by: (a) for an individual exposed to a hemodialysis

(23) $\mathrm{Kel}=\frac{\left({\mathrm{Na}}^{+}+K^{+}+{\mathrm{Mg}}^{+}+{\mathrm{Ca}}^{+}\right)\left(\mathrm{mmol}\text{/}l\right)}{142+13\left(\mathrm{mmol}\text{/}l\right)}$
and (b) for other individuals

(24) $\mathrm{Kel}=\frac{\left({\mathrm{Na}}^{+}\right)\left(\mathrm{mmol}\text{/}l\right)}{142\left(\mathrm{mmol}\text{/}l\right)};$

(25) K.sub.w is the weight coefficient, being

(26) $\frac{\mathrm{Actual}\mathrm{weight}}{\mathrm{Ideal}{\mathrm{weight}}^{*}}$
for the corresponding sex and age of the individual according to the International Table of ideal weights; and

(27) IB is the index balance.

(28) (2) Preferably, the corrected version of the above formula (1), proposed by the inventors, is used:

(29) $\begin{array}{cc}\mathrm{SV}=\frac{\Delta R.Math.\rho .Math.L^2.Math.\left(\alpha +\beta \right).Math.\mathrm{KW}.Math.\mathrm{HF}}{R.Math.R_i.Math.\beta }& \left(2\right)\end{array}$
Here, ρ is the specific resistivity of blood (ohm/cm) being the value of the hematocrit, obtained from analysis of the individual's blood (Hct), L is the individual's height (cm), HF is the hydration factor related to the body water composition, R.sub.i is the resistance (ohm) corrected basal by the coefficient K.sub.sex, age.

(30) The inventors have introduced such a correction hydration factor in order to correct the influence of the hydration state on the reliability of the stroke volume measurements. The hydration factor HF is dependent on a ratio between the measured total body water (TBW) volume and the expected individual's normal water volume. The actual TBW is measured as (4.96+0.42 L.sup.2/R) for women and (8.30+0.42.Math.L.sup.2/R) for men, where L is the individual's height and R is the measured resistance, and the TBW expected for the specific patient is typically determined as 40%-63% of the body weight for the specific patient. When the measured TBW is within a normal range, no correction is required, i.e. HF is set as 1.0. When a patient is dehydrated, which means that the measured TBW is below the above range, i.e. below 40% of the body weight, the SV would be decreased and thus needs to be corrected by the hydration factor, and similarly when the patient is over-hydrated, the measured TBW is higher than 63% of his weight, the SV would be increased and again needs to be corrected by the hydration factor. The hydration factor for such dehydrated and overhydrated states is set as, respectively, HF.sub.1=TBW.sub.meas/BL, where TBW.sub.meas is the measured value of the patient's TBW and BL is the bottom limit of the normal TBW range, and HF.sub.1=TBW.sub.meas/TL where TL is the top limit of the normal TBW range.

(31) Thus, equations (1) and (2) differ from each other in that the coefficient K.sub.sex age, which affects the basal resistance R, is represented in equation (2) by the corrected basal resistance R.sub.i, and the IB (index balance) is represented in equation (2) by the hydration factor HF. The corrected height H.sup.2corr is not included in equation (2), but in patients whose arms are disproportionately long the electrodes should preferably be placed about 5 cm proximally to their regular position.

(32) The invention utilizes the principal difference between the Hydration Factor and Index Balance consisting of the following: The hydration factor is the ΔR amplitude correction factor, while the index balance is used for assessment of patient's ideal R, prediction of which for extracellular body water included some irrelevant assumptions. The hydration factor is used only when the measured TBW for the specific patient is out of the normal range.

(33) (3) The inventors have found that the above first physico-physiological principle (volumetric change based) can be further improved by using the following formula corrected by the inventors:

(34) $\begin{array}{cc}\mathrm{SV}=\frac{\Delta R.Math.k_{\mathrm{HR}}.Math.\left(\alpha +\beta \right)}{\beta }.Math.\rho .Math.\frac{L^2}{R.Math.R_i}.Math.\mathrm{KW}.Math.\mathrm{HF}& \left(3\right)\end{array}$
where k.sub.HR is a coefficient for correction of the (a+β)/β ratio where (α+β) is the duration of a cardiac cycle, being a sum of its anacrotic and catacrotic portion.

(35) The k.sub.HR coefficient is set as follows: If the measured patient's heart rate HR.sub.meas is within the normal range, e.g. 60-100, then k.sub.HR=1, if HR.sub.meas is less than the bottom limit BL of the normal range, then k.sub.HR=BL/HR.sub.meas and if HR.sub.meas is higher than the top limit TL of the normal range, then k.sub.HR=TL/HR.sub.meas.

(36) The second physico-physiological principle is the velocimetric principle. The essence of this principle is the fact that the electrical signal of the SIV is determined by the systolic changes of the arterial blood velocity. In this algorithm, the formula for the basic variable is dR/dt multiplied by the LV ejection time T.

(37) To this end, generally the known Patterson equation

(38) $\mathrm{sv}=\frac{dR}{dt}.Math.T.Math.\rho .Math.{\left(\frac{L}{R}\right)}^2$
might be used, but with corresponding calibration factor.

(39) Preferably, however, the following equation, presenting a corrected version of the Patterson equation, proposed by the inventors, is used:

(40) $\begin{array}{cc}\mathrm{SV}=k_{\mathrm{dr}}.Math.\frac{dR}{dt}.Math.T.Math.\rho .Math.{\left(\frac{L}{R}\right)}^2& \left(4a\right)\end{array}$
or a further corrected version:

(41) 0$\begin{array}{cc}\mathrm{SV}=k_{\mathrm{dr}}.Math.\frac{dR}{dt}.Math.T.Math.\rho .Math.\frac{L^2}{R.Math.R_i}.Math.\mathrm{KW}.Math.\mathrm{HF}& \left(4b\right)\end{array}$
wherein dR/dt is the peak of the first derivative of the blood resistance change during the cardiac cycle (ohm/sec), T is the cardiac ejection time (sec) namely the time interval between the point of the systolic upstroke of the maximal slope and the minimal point of the slope, and where the parameter D being a distance between the electrodes in the Patterson equation is replaced by the height L of the patient, and where a correcting coefficient k.sub.dr (calibration factor) to the expression ((dR/dt).Math.T) is added.

(42) Currently, the volumetric algorithms are used in ICG technologies where electrodes are applied peripherally to the limbs, and the velocimetric formula is used in the thoracic approach, where electrodes are applied to the chest.

(43) The inventors have found that the use of peripheral SIV signals is more accurate than that of thoracic SIV signals for calculating the stroke volume, and that in cases with normal values of total peripheral resistance (TPR) and of cardiac index (CI), the volumetric formula is preferable for measuring the SV, whereas in cases where TPR satisfies a first predetermined condition (is higher than a certain value within a range from about 1800 dynes/sec.sup.−5 to about 1900 dynes/sec.sup.−5), and preferably also when the CI satisfies a second predetermined condition (is lower than 2.5 lit/min/m.sup.2), the velocimetric formula performs more accurately.

(44) Thus, the control system (its processing and analyzing utility) analyzes the data indicative of the patient's TPR and preferably also the CI, and decides about the model to be used for the SV calculation. The model may include separate formulas for the first and second principles underlying the calculation, namely, either one of formulas (1), (2) and (3), or formula (4a) or (4b), respectively.

(45) Alternatively, the model may include the following novel combined formula developed by the inventors with the appropriately adjusted coefficients in accordance with the TPR data and possibly also CI data:

(46) $\begin{array}{cc}\mathrm{SV}=\left[\frac{\Delta R.Math.k_{\mathrm{HR}}.Math.\left(\alpha +\beta \right)}{\beta }+k_{\mathrm{dr}}.Math.\frac{dR}{dt}.Math.T\right].Math.\rho .Math.\frac{L^2}{R.Math.R_i}.Math.\mathrm{KW}.Math.k_{\mathrm{HF}}& \left(5\right)\end{array}$

(47) In the above model (5), either one of the following parameters k.sub.HR and k.sub.dr is selectively set to value 1 or 0 depending on at least the measured individual's TPR, as described above. It should be noted that in order to measure the TPR, the control system sets the coefficient k.sub.dr to 0, and thus calculates the stroke volume based on the volumetric changes, then calculates therefrom the cardiac output, utilizes this data and the blood pressure data to calculate the TPR. Then, the control system analyzes the TPR value and preferably also the cardiac index value to identify whether the predetermined condition(s) is/are satisfied or not to respectively set the coefficients k.sub.HR=0 and k.sub.dr=1 or vice versa.

(48) The new formula (5) uses both of the electrical impedance waveform physiological sources, namely conductivity changes due to volumetric changes of blood in the arterial system during cardiac cycle assessed by the volume (ΔR) wave, and conductivity changes due to conductivity changes of the flowing blood caused by erythrocytes orientation effect during the cardiac cycle assessed by the blood flow velocity (dR/dt) wave.

(49) The technique of the present invention, based on the selective use of the appropriate calculation mode, is grounded on the peripheral displacement of the minimum two electrodes to the individual's body in a manner enabling the acquisition of electrical bioimpedance measurements of the regional part of an individual's body. Using this technique advantageously provides the current dispersion throughout an individual's/subject's/patient's body and extremities, to be reduced. The measured resistance of a part of an individual's/subject's/patient's body is increased in comparison with whole-body resistance, thus increasing the accuracy of the measured R.sub.0 and ΔR and dR/dt. The other two extremities of the patient are free for other possible treatments or measurements, or for patient's activities. The one or two extremities with local pathology may be excluded. The technique provides for body water and segmental body water distribution assessment.

(50) Thus, the present invention provides a novel system and method for calculating cardiac output through bioimpedance measurements of a patient. The system includes a bioimpedance measurement unit; electrodes' arrangement for attachment to a patient's arm and leg to provide an electrical output being in electrical communication with the resistance measurement unit; and a control system for operating the electrodes and for analyzing the electrical output. The invented technique for monitoring hemodynamic parameters is principally different from the existing systems in that the invented system includes a two-component (volumetric and velocimetric) approach providing a selective use of either one of the ΔR and dR/dt data, or possibly both of them, where ΔR.Math.(α+β)/β and dR/dt.Math.T are used interchangeably. The use of this novel approach preferably introduces a hydration factor for correction of ΔR value.

(51) The invention also provides for determining the hydration status of a patient by measuring the resistivity of the regional part of a patients body and deriving the patients hydration status. Optionally, the resistivity of the interstitial fluid in the body is measured to derive the patient's hydration status. The patient's hydration state influences the amplitude and shape of the impedance waveform, as described above.

(52) As indicated above, the measurement/monitoring system of the present invention may be configured as a tetrapolar or bipolar electrical integral bioimpedance measurement system for measuring cardiovascular parameters. The tetrapolar mode is more accurate compared to the bipolar mode, because it excludes the influence of impedance between an electrode and a patient's skin. This impedance Z.sub.skin does not provide any useful information about the cardiovascular parameters of a patient; Z.sub.skin is an interference to body impedance and is influenced by the condition of the patient's skin (whether it is oily or dry, etc.).

(53) Reference is made to FIG. 3A showing one specific but not limiting example of the configuration of the measurement unit, generally at 15A, of the present invention. It should first be noted that a human body behaves, from an electrical point of view, as a resistance-capacitance (RC) impedance. The value of impedance is influenced by the injection current frequency. This frequency is about 32 KHz. The frequency of injecting current is controlled by a direct digital syntheser (DDS) generator 1 (which is a part of the measurement unit 15A in FIG. 1A), which is in turn operated by a microcontroller 11. The output frequency and amplitude of a sinusoidal signal are controlled to be stable. This signal operates a current source 2 (at the measurement unit 15A). The current source produces an electric current of the high-stability amplitude which is applied through two electrodes E.sub.1 and E.sub.2 at locations 3 and 4, respectively, to a patient's body 5. Also preferably provided in the measurement unit is a leadoff detector 17, which is used to sense the absence of a contact between the electrode and the body.

(54) The read voltage signal, proportional to the human body impedance Z (i.e. an integral bioimpedance), is transferred from two voltage electrodes E′.sub.1 and E′.sub.2 at locations 3a and 4a respectively (+V, −V) to a high precision instrumentation amplifier 6, the output of which is fed to the first input of a synchronous detector 7. The latter has two functions: (1) it rectifies the obtained integral bioimpedance signal; and (2) it provides simultaneous derivation of the active component R of the integral bioimpedance signal vector. This component is directly proportional to the resistive component of the lead (resistance of the blood system). Linearity of the synchronous detector 7 simplifies the calibration process and reduces it to a single-step initial adjustment (instead of a per cycle calibration).

(55) The output of detector 7 is connected to a low frequency filter 8 which may for example be a low pass Bessel filter. Filter 8 cuts off high frequency components, for example above 32 KHz, and delivers an operating signal, which has the active bioimpedance component (DC) R, and the waveform bioimpedance signal (AC) ΔR. The operating signal is input to R Scale Amplifier 9 and to Bioamplifier and Filter 10. Amplifier 9 produces an output signal proportional to the active bioimpedance component R and transmits the same to an input ADC (Analog-to-Digital Converter) of the microcontroller 11. Bioamplifier and Filter 10 separates from the operating signal the waveform ΔR component. The output of the Bioamplifier and Filter 10 is connected to another input ADC of microcontroller 11. The latter communicates with a HOST processor (data processing and analyzing utility 18B of control system 18 in FIG. 1A) which is not shown here.

(56) FIG. 3B further exemplifies the configuration of the measurement system of the invention. Here, three additional ECG electrodes are used being applied to the chest of a patient and connected to an ECG measurement circuit 20. The measurement system includes a measurement unit (15A in FIG. 1A) and a control system (18 in FIG. 1A). The latter is represented in FIG. 3B by a HOST processor 21. The measurement unit includes a bioimpedance signal receiver unit 19 and a microcontroller 11 (such as model ADuC814 commercially available from Analog Device®), which combines the functions of an A/D converter and a microprocessor, and operates for real time processing of first data or curve (which is a composition of direct “R” and alternating “ΔR” components of an active bioimpedance signal obtained from the bioimpedance receiver unit 19, together with second data (curve) obtained from the ECG circuit 20. Additionally, microcontroller 11 preferably also receives data indicative of the detected leadoff condition with regard to all the electrodes including those of the bioimpedance measuring unit 15A (bio leadoff) and those of the ECG measurement circuit (ECG leadoff).

(57) The outputs of microcontroller 11 are connected to HOST processor 21 of the control system via an isolation data unit 22 (such as opto-isolators HCPL2611HP®) providing electrical protection of the patient from high voltage, via a Driver circuit 23 (such as the driver RS232C or USB) and interface utility 24 (via wires or wireless). The entire system is power supplied (e.g. +5V) from the host processor via an isolating DC/DC circuit 25 and further a power supply unit 27 which stabilizes the voltage value.

(58) Reference is made to FIGS. 4A to 4C exemplifying a method of the present invention for determining a patient's stroke volume. To facilitate understanding, the same reference numbers are used for identifying the common steps in the flow charts of FIGS. 4A-4C.

(59) Measurements are taken on the patient using the electrodes' arrangement (of either one of FIGS. 1A and 2A) to obtain the electrical output (step 101).

(60) In the example of FIG. 4A, additionally, the patient's heart condition is analyzed to identify whether the acute heart failure (AHF) condition exists or not (step 104). If this condition exists, then the electrical output data is processed (at the HOST processor) to determine the SV value based on the dR/dt function (step 108a), and if the condition is not identified the HOST processor operates to process the electrical output data to determine the SV value based on the dR/R function (step 108b). As indicated above, this selective processing includes using either one of formulas (1)-(3) or setting the coefficients k.sub.dr and k.sub.HR in formula (5) for the ΔR/R function based measurements; or using formula (4a) or (4b) or setting the coefficients k.sub.dr and k.sub.HR in formula (5) for the dR/dt function based measurements.

(61) In the example of FIG. 4B, data indicative of the patient's TPR is provided (step 102). As shown in the figure, this data may be independently provided (step 102). Preferably, as shown in the figure, this data may be obtained by calculation: using the cardiac output dR/R form the same measured data indicative of the electrical output (step 103a) and a separate measurement of the patient's blood pressure (step 103b) and calculating the TPR being a function of these two parameters (step 103c). Then, the TPR data is analyzed at the HOST processor (step 104) to determine whether the TPR value satisfies a first predetermined condition, to apply selective processing to the electrical output data. This condition sets the TPR value to be about 30% higher than the top limit of the normal range (which is about 750-1500 dynes.Math.sec.Math.cm.sup.−5), e.g. TPR being above a certain value within a range from about 1800 dynes/sec.sup.−5 to about 1900 dynes/sec.sup.−5, e.g. being above 1800. If this condition is satisfied, then the electrical output data is processed (at the HOST processor) to determine the SV value based on the dR/dt function (step 108a), and if the condition is not satisfied the HOST processor operates to process the electrical output data to determine the SV value based on the dR/R function (step 108b). As indicated above, this selective processing includes using either one of formulas (1)-(3) or setting the coefficients k.sub.dr and k.sub.HR in formula (5) for the dR/R function based measurements; or using formula (4a) or (4b) or setting the coefficients k.sub.dr and k.sub.HR in formula (5) for the dR/dt function based measurements.

(62) FIG. 4C shows yet another example of a method of the present invention. The example of FIG. 4C differs from the previous examples in that the selective processing is based, additionally or alternatively to the examples of FIGS. 4A and 4B, on determination of a cardiac index CI (step 105), derived from the measured cardiac output as CI=(ΔR/R)/BSA, BSA being the body surface area, and analyzing whether the cardiac index CI satisfies a second predetermined condition, which is used alternatively or additionally to the analysis of the TPR value (step 104′). According to this second condition, the CI is below 2.5 lit/min/m.sup.2. If this condition is satisfied (alone or together with the above-described first condition), the electrical output data is processed to determine the SV value based on the dR/dt function (step 108a), and if the condition is not satisfied, the electrical output data is processed to determine the SV value based on the ΔR/R function (step 108b).

(63) The following are some examples of the experimental data showing the features of the present invention:

(64) Tables 1 and 2 below show the SV measurement results of 16 patients, AS23-AS38, with acute heart failure (group A) and of 29 ICU patients WS26-WS54 after coronary surgery (group B) by volumetric and by velocimetric approaches as compared with their concomitant thermodilution (TD) SV results.

(65) TABLE-US-00001 TABLE 1 Cardiac Index SV SV Diff % SV Diff % lit/min/m.sup.2 TD ΔR ΔR vs dR/dt dR/dt vs TPR Pt No Sex Age TD NIC Cc cc TD cc TD (dyne .Math. sec .Math. cm.sup.−5 AS 23 F 65 3.3 3.8 68 76 +12 64 −6 1607 AS 24 F 90 1.8 1.8 38 38 0 41 +8 4026 AS 25 M 60 2.3 2.4 59 60 +1.7 79 +34 1857 AS 26 M 78 1.1 0.6 24 16 −33 26 +8 2100 AS 27 M 74 1.9 1.9 46 54 +17 43 −7 1890 AS 28 M 66 2.0 1.9 78 74 −5 79 +1 2455 AS 29 F 66 2.2 2.6 54 63 +17 64 +18 1527 AS 30 M 66 2.7 2.8 60 54 −10 55 −8 1485 AS 31 M 67 2.7 2.2 69 53 −23 72 +4 1900 AS 32 M 62 1.7 1.2 62 47 −24 68 +10 4561 AS 33 F 76 3.0 3.0 98 90 −8 109 +11 1741 AS 34 M 79 2.2 2.6 51 64 +25 61 +20 1826 AS 35 F 75 2.5 3.3 66 64 −3 66 0 1550 AS 36 M 89 1.7 1.3 48 35 −27 40 −17 3806 AS 37 M 86 1.4 1.0 32 25 −22 30 −6 2900 AS 38 F 70 2.2 1.8 44 38 −14 38 −14 2586

(66) TABLE-US-00002 TABLE 2 Cardiac Index SV Diff % Diff % lit/min/m.sup.2 SV ΔR ΔR vs SV dR/dt vs TPR Pt No Sex Age TD CI NI CI TD cc cc TD dR/dt TD (dyne .Math. sec .Math. cm.sup.−5) WS 26 F 74 5.4 5.6 106 117 +10 89 −16 706 WS 27 F 67 2.1 1.8 43 37 −14 44 +2 2510 WS 28 M 79 2.6 2.4 56 56 0 54 −4 1505 WS 29 M 70 2.2 2.4 39 39 0 36 −8 1625 WS 30 M 52 4.4 3 64 54 −16 64 0 1001 WS 31 M 70 4.2 4.4 58 70 +21 67 +16 1163 WS 32 F 88 1.6 1.5 35 31 −11 35 0 4164 WS 33 F 74 2.6 2.8 42 50 +19 48 +14 1926 WS 34 M 60 2.2 2.4 52 52 0 47 −10 1805 WS 35 M 54 3.3 3.6 59 62 +5 54 −9 1142 WS 36 M 62 3.7 3.9 88 77 −12 73 −17 1151 WS 37 M 55 3.3 3.3 68 65 −4 55 −19 906 WS 38 M 72 2.2 2.4 59 54 −8 59 0 1696 WS 39 M 65 2.9 2.9 55 53 −4 55 0 1031 WS 40 M 76 2.2 2.3 39 37 −5 42 +8 1376 WS 41 M 57 3.8 4.1 80 74 −7 85 +6 746 WS 42 F 75 3.1 3.2 48 50 +4 52 +8 1475 WS 43 F 79 2.5 2.5 56 56 0 58 +4 1499 WS 44 M 53 4.6 4.5 85 79 −7 71 −16 711 WS 45 F 76 1.8 1.9 36 37 +3 44 +22 1436 WS 46 M 62 3.8 4 54 54 0 53 −2 897 WS 47 M 68 4.3 4.2 85 73 −14 98 +15 900 WS 48 M 55 3.1 3 58 57 −2 67 +15 1571 WS 49 M 88 3.3 3 68 64 −6 73 +7 1509 WS 50 F 75 2.7 3 63 70 +11 66 +5 1406 WS 51 M 47 4.9 4.9 105 104 −1 79 −25 654 WS 52 M 77 1.6 1.7 28 27 −4 28 0 2662 WS 53 F 64 1.9 1.8 35 36 +3 32 −9 2251 WS 54 F 54 3.7 3.8 71 68 −4 78 +10 1313

(67) When in group A (Table 1) the total peripheral resistance (TPR) was equal or higher than 1900 dyne.Math.sec.Math.cm.sup.−5, the ΔR-based SV results were significantly underestimated (lower by 18% versus TD), whereas the dR/dt-based results were in good agreement with TD values. However, in group A, where TPR was lower than 1900 dyne.Math.sec.Math.cm.sup.5, as well as in the entire group B, ΔR- and dR/dt-based results were in good accordance with the thermodilution SV results. It is thus evident that in acute heart failure, measuring the SV is substantially more reliable by the peripheral velocimetric rather than by the volumetric ICG formula. This is in contrast to post-open-heart ICU results, where the volumetric formula performs better. While the present invention has been described with the reference to the attached drawings, it should be appreciated, that other embodiments of the described system and its elements can be suggested and should be considered as part of the invention.