DE1498534C - Method and device for determining the dilution of dye in the blood, in particular for the purpose of determining cardiac output - Google Patents

Description

3 4

flat bodies, which are measured depending on the flow determination of the dye dilution

speed different to the direction of flow. This makes it possible to use freely selectable test

orientation). When measuring the light absorbing dyes, measurements are taken in the cuvette or on the ear

tion at the ear, this flow influence is ignored, carried out by both fluctuations in the

lent; on the other hand, there are noticeable influences of 5 O ₂ saturation as well as fluctuations in the con-

due to changes in concentration, layer thickness and flow factor that are dependent on blood pressure

Layer thickness that does not apply to the cuvette measurement. are independent.

The invention is based on the object of providing a

To create a process of the type mentioned at the outset, clearly. It shows

the O ₂ -saturation-independent measurements also except- io F i g. 1 the extinction curves of various tests half of the natural isosbestic point allow dyes,

light. Such a process would also show FIG. 2 the absorbance curves of reduced

Giving the possibility of a compensation also of the hemoglobin Hb, oxidized hemoglobin HbO ₂ and

other interfering influences due to fluctuations in the condensation test dye methylene blue,

centering, the layer thickness and the flow 15 F i g. 3 the values of the absorbance from the absorbance

factor with several isosbestic measured values tion curves according to FIG. 2 for two different

to be carried out by measuring light waves and wavelengths derived from these values

lengths to be selected appropriate for the test dye sizes,

much more different sensitivities. 4 the absorbance curves of reduced

as for the natural blood pigments. so hemoglobin Hb, oxidized hemoglobin HbO ₂ and

Based on this consideration, the test dye cardio green,

according to the compensation of the fluctuations F i g. 5 the values of the extinction from the extinction

the degree of O ₂ saturation for absorbance measurements. tion curves according to FIG. 4 for two different

outside the natural isosbestic point, the wavelengths and those derived from these values

Extinctions at two selected light waves - 25 sizes and

length of the blood measured and the O ₂ saturation F i g. 6 shows the basic circuit diagram of a device

dependent proportions of these extinctions before the addition of the invention.

To determine the cardiac output by Injek setting the sensitivities when a test dye is introduced into the bloodstream and selected light wavelengths made the same size and compensated for photometric measurements of the light absorption of the blood colored by calculating the difference between the two absorbances in selected areas of the circle and then the changes are made, it is customary to use two different shades of this O ₂ saturation-independent extinction substance group. One representative for the one color difference value after adding a substance of different size is methylene blue, the absorption maxima of which are extinctions for the two selected light values between λ = 600 and 660 πΐμ; a representative of the test dye for the second group is the dye cardio green, the mood of the dye dilution is measured. whose maximum is around λ - 800 πΐμ and des- In this way it is possible to O ₂ saturation sensitivity extends into the range of the red independent measurements of light absorption and light; The absorption curves of these and other dyes outside the natural isosbestic point 40 are to be carried out in FIG. 1 of the drawing and test dyes which are reproduced are to be used.

In the natural isosbestic point, no useful results can be obtained from the photometric measurement of the light-absorbable measurement results. tion in the blood one maintains the logarithm of the trans-Furthermore, the new method offers the advantageous mission as a so-called extinction value E to show the interfering influences of fluctuations in order to a linear representation of the concentration in the blood, the layer thickness to reach concentrations of dye contained measurement on the ear and the flow when measuring in the Kü- the values of the light absorption or extinction vette to compensate, characterized in that in a further development not a second O ₂ -sättigungsunabhängiger only of the injected test dye special invention which also includes of the natural blood pigments, the extinction value, either the extinction 50 dependent; As a result, they are subject to interfering influences, value at the natural isosbestic point or which are due to fluctuations in light absorption by a second, from the extinction values at two other - these natural blood pigments, the selected light wavelengths according to the main cause of the extinction fluctuations are derived from the described method O ₂ -saturation- the changes in the oxygen saturation of the blood, independent absorbance difference value is formed, 55 in F i g. 2, the absorbance values are that the of concentration, film thickness and currents contained self-dye components Hämomungsfaktor dependent components of the globin Hb and oxyhemoglobin HbO ₂ thus formed, shown for the blood, both O ₂ -sättigungsunabhängigen absorbance values of the oxygen saturation of the blood it depends, in the addition of the test dye through the ratio of these two natural color settings of the sensitivities equal to 60 substances to one another. The extinction of the can be made practically large and compensated for by forming the difference between these always existing mixtures of these two natural extinction values and that borrowed blood pigments always lie between the two, the changes in this from fluctuations in both curves Hb and HbO ₂ . Only for the wavelength A _{0 of} the O ₂ saturation and the concentration, the - 805 πΐμ, the extinction is the same for both dye component layer thickness and the flow factor independent 65 component hemoglobin and oxyhemoglobin. The extinction difference value after adding an un- change in the oxygen saturation, by means of which the equal extinctions at the selected ratio of these two blood dyes to one another is determined for the test dye having light wavelengths, thus have at the wavelength X ₀

5 6

== 805 πΐμ no influence on the extinction. Around portions b _x and b ₂ embody a ratio O ₁ Zb ₂

of the oxygen saturation or the different ■ = F ₂ , in the example equal to 2, 6, that for any

borrowed extinctions for arterial and venous blood oxygen saturation, since these proportions change when

to be independent, one uses this point of intersection of the oxygen saturation only proportional changes

or so-called isosbestic point of the two 5 ranks, is unchangeable and only

Extinction curves Hb and HbO ₂ for arterial and depends on the choice of the two wavelengths A ₁ , A _2,

venous blood. For deriving an oxygen saturation-independent

Now, however, the extinction through the blood-colored extinction values can be determined by the extinction substances not only on the oxygen saturation of the value E ₁ at X ₁ with F ₁ = 1 and the extinction _{value E 2 of} blood, but also on a further 10 at X ₂ multiply by F ₂ = O ₁ Ib ₂ = 2.6, which means that the factors, in particular of the concentration C of the oxygen saturation-dependent proportions of the blood pigment thus removed, of the thickness D of the extinction values at X ₁ and A _{9 based} on the extinction are the same measurement used blood-perfused layer that will be. This process is shown in FIG. 3 related to measurements, e.g. B. at the ear, fluctuations, especially from I to II illustrated. Due to the subsequent special due to the changing blood pressure, 15 subtraction of the extinction values derived in this way is subjected and depends on the measurement in a one holds an extinction difference value, which is proportional to the flow rate of the per-cuvette
Blood.

Fluctuations in the concentration of the blood color i ^E z "F ₂ ~ ^E i · F ₁ )
substance with constant oxygen saturation, constant 20

Layer thickness D and constant flow rate and oxygen saturation is independent, since the acidic

a proportional increase or saturation-dependent proportions caused by the sub-

took out the absorbance values. Fluctuations. traction disappear, the extinction components
the layer thickness D also have a proportional effect

Shifts in curves Hb and HbO ₂ . These 25 ^a i - E _{lRh02 and a 2} = E _2MhO2
Fluctuations play a particularly important role

when taking measurements on the earlobe. are not influenced by the oxygen saturation

Fluctuations in the flow velocity and the quotient F ₂ = b ₁ lb _{2 are} also fixed, only

when measuring on a cuvette lead to proportionally due to the selection of the wavelengths A ₁ and A ₂

nal shifts of the extinction values with otherwise 30 correct constant. From the corresponding

influencing variables kept constant. the compensation process of the measurement results

According to the invention, oxygen saturation and oxygen saturation-independent, difference-independent absorbance measurements, not just in terms of value, can be carried out

natural isosbestic point, but also at ^ = F · Ε - F · E - 26E - E

perform other wavelengths by mau the 35 ^lp2 2211 »21 ·

different influences of oxygen saturation With the derivation of this oxygen saturation-independent

compensated for two selected wavelengths. The corresponding absorbance difference value <5 _{1> 2} is now available

with the later introduction of the test dye two absorbance independent of oxygen saturation

not also a compensation of the extinction values, the extinction difference value d _lw 2 and the extinction

of the test dye at the selected two 40 tion values E ₁ at A ₁ and E ₂ at A ₂ derived pri-

Wavelengths takes place, it is important to note the two mär extinction difference value <S _li2 and the extinction

Select wavelengths in such a way that the conversion value E ₀ at the natural isosbestic point

used test dye as different as possible for the wavelength A ₀ . From these two oxygen

Absorbances result which become easily measurable absorbance-independent extinction values

lead values. 45 now to compensate for the influences of

F i g. 2 and 3 illustrate the compensation concentration, layer thickness and flow velocity

sationsverf ahren according to the invention when using the same extinction values initially equal

of methylene blue as a test dye. For this color measure F i g. 3 III derived from the fact that the ex-

to derive an oxygen saturation reduction value E ₀ = Q ₀ at A ₀ with one

independent absorbance value two wavelengths 50 factor
A ₁ = 660 πΐμ and A ₂ = 760 πΐμ selected. the

Wavelength A ₁ is at the extinction maximum of F ₀ ⁼ ( ^a 2 "F ₂ ~~ ^α ι) / ^β ο ⁼ 1> 45
Methylene blue, while the extinction by methylene blue at the wavelength A ₂ is multiplied very much less (Fig. 3, IV) that the equation is than for X ₁ . From Fig. 2 are the extinction components
elements F ₀ ' ^E o + ^F i' ^E i ~ F ₂ " ^E z

a _x - E ₁ Hb ₀₂ and a ₂ = E _2m02 for 100% HbO ₂ and. ... _ _c

u _ ε · r. 1it τ? c ~ inr> / τττ. is satisfied. By then subtracting the so

«! O + ₁ - E ₁ a or a ₂ + b ₂ = E _2Kb for 100 »/ 0 Hb _gewoI1 nenen equal absorbance values obtained

refer to. The oxygen saturation dependent 60 is a secondary difference value ■

5 _{1) 2}

-F ₁ . E ₁ -F ₀ -E ₀ = 2.6E ₂ -E ₁ -1.45E ₀ = O

with compensation of all, from the natural course of a for these compensation processes

Absorbances resulting from blood pigments. In this case, none of the four above-

thus also the other influences on the named ones, the extinction by the natural ones

Absorbance due to the natural blood pigments for coloring factors determining factors more noticeable

the end result obliterated so that what matters is. As long as no test dye is supplied

at the output of the measuring device there is neither a change in oxygen saturation nor in concentration nor in layer thickness nor in flow rate, but probably after the introduction of the test dye, since its influences are not compensated for by the compensation processes described, in particular not because methylene Blue at A ₀ in the natural isosbestic point P practically none at all, at X ₁ , A _2, on the other hand, causes a high extinction.

The above numerical values for the factors F ₁ , F ₂ , F _{0 to} be used for compensation apply to cuvette measurements. For indirect measurements, e.g. B. Measurements at the ear, the same considerations apply, only a further value for the light absorption of the tissue must be added to all sum values of the extinction. The fabric behaves practically like a gray filter.

4 and 5 illustrate the analog measuring and compensation process for the wavelengths X ₀ , A ₃ and A ₄ in connection with the test dye cardio green. Here, from the extinction values E ₃ , E ₄ at the wavelengths X ₃ and A ₄ , a primary extinction difference value δ _{3Λ, which is artificially made independent of oxygen saturation, is} derived again by compensation, which is then combined with the natural oxygen _{saturation-independent extinction value E 0} for the isosbestic point at A ₀ by compensation _{Derivation of a secondary extinction difference value} that is independent of oxygen saturation, concentration, layer thickness and flow velocity is used. The corresponding compensation equations are:

^ 3,4 ^{= F} i ' ^E i ~ ^F 3 ~ ^E 3> ^F i ⁼
O-SA ^{= δ} 3Λ ~ ^F 0 ' ^E 0> ^F 0 ⁼ (

^F 3 ~

To carry out the method of the described measurements with three light wavelengths A ₁ , A ₂ and A ₀ or A _3t, A ₄ and A ₀ , a device according to FIG. 6 can be used. It consists of a light source L with a broad spectrum, a cuvette K or the organic test object, three monochromatic filters F, photocells Z as light intensity indicators, logarithmic amplifiers V _L or other suitable networks that allow the values of light absorption according to Beer's law Logarithmization into values of the extinction, and for each light wavelength A to be evaluated from a display instrument A, which is preceded by an adjustable multiplier, for example in the form of an arithmetic amplifier V _{K of} adjustable amplification. After linking in a difference-forming network N _n according to the method steps described above, the combination of the result displayed separately in the display instrument A for each spectral component of interest is combined to form the difference value of interest and displayed in the recording or measuring device R for evaluation.

The filters F must meet the respective requirements of the process for a particular dye. They would, based on the first example (methylene blue) presented above, for the light wavelengths A ₁ = 660 ΐημ, A ₂ = 760 πΐμ and A ₀ = 805 ΐημ, based on the second example (cardio green), for A. ₃ = 900 ηΐμ, A ₄ = 990 πΐμ and A ₀ = 805 πΐμ.

The required monochromaticity can be increased by choosing photo cells Z with a suitable sensitivity spectrum. The three values of the extinction obtained in this way, which are displayed in the display instruments A , are then interconnected by a selection switch within the network N _D so that sum or difference _{values <5 12} or <5 _{34 of} the extinctions are formed from two systems will. Such a primary difference _{value <5 12} or O ₃₄ then again allows a difference to be formed with the value of the extinction E ₀ . to obtain the secondary difference <5 _{01> 2} or <S _{0> 34} . If the latter, by setting the computing amplifier V _R accordingly, becomes zero, the result in the measuring device R remains with O ₂ saturation

as well as with changes in concentration, layer thickness and flow velocity and only responds to the selected test dye. This corresponds to the idea of the invention continuous compensation of the disturbing effects is possible.

1 sheet of drawings

Claims (3)

1 2 common downstream differential-forming patent claims: the network (ND). 4. Apparatus according to claim 3, characterized in that 1. Method for determining the dye indicates that the multiplier thinning in the blood, especially for the purpose of determination 5 (F ^) from a computer amplifier with adjustable beam the cardiac output, by means of photometric amplification. shear measurement of light absorption by a test dye added to the blood in one Flow-through vessel, characterized in that the invention relates to a method and net that to compensate for the fluctuations io a device for determining the dye ratio the degree of O ₂ saturation for extinction measurements in the blood, in particular for the purpose of determination gene outside the natural isosbestic of the cardiac output, using photometric measurement Point (λ ₀ = 805 πΐμ) with two selected solutions of light absorption by one of the blood Light wavelengths the extinctions (E) of the test dye set in a flow-through vessel, tes measured and the 0 ₂ -saturation-dependent 15 To carry out this measurement it would be Proportions of these extinctions prior to addition are desirable to reduce light absorption during the of the test dye due to different measurement only fluctuations due to the injected setting of the sensitivities in the case of the test dye would be subject; actually subject Chose light wavelengths the same size made the light absorption but also other swan and by forming the difference between the two extinctions which indicate the presence of the natural that the blood pigments hemoglobin Hb and oxyhemoglobin change This O ₂ saturation-independent extink HbO _{2 can be} traced back to wrestling. The light absorption is tion difference value after adding an un- both from the concentration and in particular equal extinctions for the two, depending on the one dependent on _{the respective O 2 saturation} Chose a test with wavelengths of light- 25 ratio of the two blood pigments Hb / HbO, from- dyestuff to determine the dyestuff diluent. Only at one wavelength of light, namely the can be measured. Wavelength λ = 805 πΐμ, the so-called isosbesti- 2. The method according to claim 1, characterized in that the light absorption is independent of the fact that to compensate for the ratio of the two blood pigments to one another. The human ear uses this isosbestic point of the so-called tors (when measuring a body vessel such as terial and venous blood to be independent of fluctuations in the concentration, the layer thickness) and the flow factor in a flow cuvette) an extinction curve for arterial and venous blood second 0 ₂ -saturation-independent extinction- from. The natural isosbestic point is only worth it, either the extinction value at 35 in connection with such test dyes for the natural isosbestic point or a need that at the wavelength λ ₀ = 805 πΐμ of the second, from the extinction values at two anisosbestic Point a well-measurable absorption whose selected light wavelengths have after. _{This applies in particular to the 0 2} -sät- test dye measurements derived up to now for the method according to claim 1, which, as shown in FIG. 1 it is shown that the concentration, layer borrowed, at the wavelength X ₀ - 805 ΐημ has a special and flow factor dependent proportions of this high sensitivity. The dye of the two O ₂ -saturation-independent methylene blue formed in this way, on the other hand, practically does not absorb the light of the white extinction values before the addition of the test length A ₀ = 805 τημ and can deselect the dye through different settings of the 45 half with conventional use of the test color -Sensitivities made the same and by measuring the substance in the natural isosbestic point differentiating these two extinction values are not used, although it is compensated for because of its low toxicity and that the changes in low toxicity and its value for money are due to fluctuations in both the O ₂ -SaUi advantages. One therefore often dispenses with the supply and the concentration, the layer 50 the advantages of the measurement in the natural isosbestidicke and the flow factor independent point and works in the light wave range, the extinction difference value after adding a high sensitivity for methylene blue, must be unequal large _{Accept the extinctions in the test dyes of the O 2} saturation which are selected but have the disadvantages of being heavily dependent on the wavelengths of light wavelengths. fes for determining the dye dilution. 55 Another significant disadvantage of the previous one will measure. Procedure for measuring dye dilution 3. The device for carrying out the method is that the measurement is also subject to errors according to claim 2 with a light source, which is subject to fluctuations in the light-absorbed spectrum and a point placed in its beam path through the natural blood pigments is one of the 60, which can be traced back to influences other than the fluctuation of the blood with the test color contained therein due to _{the O 2 saturation.} One of these flowing vessels, a photoelectric wall fluctuations, results from the aforementioned influence of changes in the concentration, characterized by at least three separate beam paths, of the natural blood pigments. When measuring with a monochromatic filter (F), 65 each of the light absorption in a flow-through cuvette under a photoelectric converter (Z) with subsequent light absorption influences due to the connected logarithmic amplifier (V _L ) changing behavior of the dye carriers in the blood and multiplication device (F ^) and a flow (the dye carriers are known to be