U.S. patent application number 13/722629 was filed with the patent office on 2013-08-15 for method and a device for determining the hydration and/or nutrition status of a patient.
This patent application is currently assigned to FRESENIUS MEDICAL CARE DEUTSCHLAND GMBH. The applicant listed for this patent is FRESENIUS MEDICAL CARE DEUTSCHLAND GMBH. Invention is credited to Paul Chamney, Peter Wabel.
Application Number | 20130211278 13/722629 |
Document ID | / |
Family ID | 34958009 |
Filed Date | 2013-08-15 |
United States Patent
Application |
20130211278 |
Kind Code |
A1 |
Chamney; Paul ; et
al. |
August 15, 2013 |
Method and a device for determining the hydration and/or nutrition
status of a patient
Abstract
The invention relates to the field of monitoring the hydration
and/or nutrition status of a patient. According to the invention a
method is provided to determine at least one of a mal-hydration
component, an adipose tissue component and a lean tissue component
of a patient comprising the steps of determining chemical or
physical properties of the patient and deriving the at least one
component on the basis of the determined chemical or physical
properties of the patient and previously determined values of a
mass or volume fraction of water in lean tissue and a mass or
volume fraction of water in adipose tissue. The invention also
relates to a device for carrying out the method according to the
invention and to a computer program product to be used on such a
device.
Inventors: |
Chamney; Paul; (Herts,
GB) ; Wabel; Peter; (Darmstadt, DE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
FRESENIUS MEDICAL CARE DEUTSCHLAND GMBH; |
|
|
US |
|
|
Assignee: |
FRESENIUS MEDICAL CARE DEUTSCHLAND
GMBH
Bad Homburg
DE
|
Family ID: |
34958009 |
Appl. No.: |
13/722629 |
Filed: |
December 20, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11630965 |
Dec 28, 2006 |
8340754 |
|
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PCT/EP2004/014544 |
Dec 21, 2004 |
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13722629 |
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Current U.S.
Class: |
600/547 |
Current CPC
Class: |
A61B 5/1073 20130101;
A61B 5/4872 20130101; A61B 5/7278 20130101; A61B 5/4869 20130101;
A61B 5/0537 20130101 |
Class at
Publication: |
600/547 |
International
Class: |
A61B 5/053 20060101
A61B005/053; A61B 5/107 20060101 A61B005/107; A61B 5/00 20060101
A61B005/00 |
Foreign Application Data
Date |
Code |
Application Number |
Jun 29, 2004 |
EP |
PCT/EP04/007023 |
Claims
1. A method to determine at least one of a mal-hydration component,
an adipose tissue component and a lean tissue component of a
patient comprising the steps of: determining chemical or physical
properties of the patient and deriving the at least one component
on the basis of the determined chemical or physical properties and
previously determined values of a mass or volume fraction of water
in lean tissue and a mass or volume fraction of water in adipose
tissue.
2. The method according to claim 1 characterised in that the at
least one component is the mass of that component of the
patient.
3. The method according to claim 1 characterised in that the at
least one component is the volume of that component of the
patient.
4. The method according to claim 1 characterised in that the
chemical or physical properties of the patient comprise at least
one of the whole body mass, the lipid mass and the total bone
mineral content mass of the patient.
5. The method according to claim 1 characterised in that the
chemical or physical properties of the patient comprise the volume
or mass of at least one of the total water, the extracellular water
and the intracellular water of the patient.
6. The method according to claim 1 characterised in that the
previously determined values comprise the mass or volume fraction
of the total water in lean tissue and the mass or volume fraction
of the total water in adipose tissue.
7. The method according to claim 1 characterised in that the
previously determined values comprise the mass or volume fraction
of extracellular water in lean tissue and the mass or volume
fraction of extracellular water in adipose tissue.
8. The method according to claim 1 characterised in that the
previously determined values comprise the mass or volume fraction
of intracellular water in lean tissue and the mass or volume
fraction of intracellular water in adipose tissue.
9. A device for carrying out the method according to claim 1
comprising: a measurement and/or input unit (5) configured to
provide values for the chemical or physical properties of the
patient to be determined, an evaluation unit (1) configured to
derive the at least one component on the basis of the determined
properties of the patient and previously determined values of a
mass or volume fraction of water in lean tissue and a mass or
volume fraction of water in adipose tissue and a communication link
between the measurement and/or input unit and the evaluation
unit.
10. The device according to claim 9 characterised in that the
evaluation unit is also configured to control the measurement
and/or input unit for determining at least one of the chemical or
physical properties of the patient.
11. The device according to claim 9 characterised in that the
evaluation unit is a microprocessor unit which in turn comprises a
microprocessor program storage unit, wherein in the microprocessor
program storage unit a program for deriving the at least one
component on the basis of the determined chemical or physical
properties of the patient and previously determined values of a
mass or volume fraction of water in lean tissue and a mass or
volume fraction of water in adipose tissue is stored.
12. The device according to claim 11 characterised in that the
program stored in the microprocessor storage unit also controls the
measurement and/or input unit for determining at least one of the
chemical or physical properties of the patient.
13. The device according to claim 9 characterised in that the
measurement unit comprises a bioimpedance measurement means to
determine at least one of the chemical or physical properties of
the patient.
14. The device according to claim 13 characterised in that the at
least one of the chemical or physical properties of the patient
comprise at least one of the extracellular water volume, the
intracellular water volume or the total body water volume of the
patient.
15. The device according to claim 1 characterised in that the
measurement unit comprises scales to determine at least one of the
chemical or physical properties of the patient.
16. The device according to claim 15 characterised in that the at
least one of the chemical or physical properties is the whole body
mass of the patient.
17. The device according to claim 9 characterised in that it
further comprises an output unit linked to the evaluation unit for
outputting, preferably displaying, any data derived by the
evaluation unit.
18. A computer program product characterised in that it comprises a
storage medium on which a microprocessor program to be stored in
the microprocessor program storage unit of the device according to
claim 11 is stored.
Description
[0001] This application is a continuation of application Ser. No.
11/630,965, filed Dec. 28, 2006, which is a nationalization of
PCT/EP2004/014544 filed Dec. 21, 2004 and published in English,
which claims priority from PCT/EP2004/07023, filed Jun. 29,
2004.
[0002] The invention relates to the field of monitoring the
hydration and/or nutrition status of a patient.
[0003] The kidneys carry out several functions for maintaining the
health of a human body. First, they control the fluid balance by
separating any excess fluid from the patient blood volume. Second,
they serve to purify the blood from any waste substances like urea
or creatinine. Last not least they also control the levels of
certain substances in the blood like electrolytes in order to
ensure a healthy and necessary concentration level.
[0004] In case of renal failure ingested fluid accumulates in body
tissues and the vascular system causing increased stress on the
circulatory system. This surplus fluid has to be removed during a
dialysis treatment by ultrafiltration of the blood. If insufficient
fluid is removed the long term consequences can be severe, leading
to high blood pressure and cardiac failure. Cardiac failure itself
is many times more likely to occur in dialysis patients and it is
thought that states of fluid overload are one of the major
contributing factors. Removal of too much fluid is also dangerous
since the dialysis patient becomes dehydrated and this invariably
leads to hypotension.
[0005] The dry weight (for the sake of simplicity the words
"weight" and "mass" shall be used synonymously throughout this
patent application document--which also is usual practise in the
medical field) defines the weight of a patient that would be
achieved if the kidneys were working normally. In other words this
represents the optimal target weight (or fluid status) which should
be achieved in order to minimise cardiovascular risk. Dry weight
has always been an elusive problem in routine clinical practise due
to lack of quantitative methods for its assessment. Currently the
dry weight problem is approached using indirect indicators like
e.g. blood pressure, echocardiographic investigations and
subjective information such as X-rays. Furthermore it has been
particularly difficult to define a set of conditions which are
universally accepted as the dry weight standard.
[0006] A promising method to derive the fluid status of a patient
involves the use of bioimpedance measurements. A small alternating
current is applied to two or more electrodes which are attached to
a patient and the corresponding electric potential difference is
measured. The various fluid compartments of a human body contribute
differently to the measured signals. The use of multiple
frequencies allows the water in the intracellular volume (ICV) and
the extracellular volume (ECV) to be determined. An example of such
a device is described in the international patent application WO
92/19153. However, this document discloses no method regarding how
the dry weight of the particular patient can be derived.
[0007] U.S. Pat. No. 5,449,000 describes a bioimpedance system also
using multiple frequencies to determine water mass in the ECV and
ICV. Furthermore certain population dependent data are taken for
using and choosing so-called population prediction formulas. The
body composition is then analysed by using these formulas and with
the help of segmental bioimpedance signals.
[0008] The international patent application WO 02/36004 A1
describes a method and a device for deriving the dry weight of a
patient with renal failure using a bioimpedance device by
extrapolating an excess water volume in the extracellular volume to
a condition where there would be no renal failure. By a similar
procedure a mass correction term accounting for deviations within
healthy human beings and being attributed to certain tissues can be
derived.
[0009] The international patent application WO 03/053239 A1
discloses a compartmental model which addresses the variation in
healthy human beings in certain body compartments in order to
better separate a mal-hydration volume and other tissue components
in particular with the aid of bioimpedance measurements. With such
a device information on the nutrition status of a patient can also
be obtained.
[0010] U.S. Pat. No. 6,615,077 describes an approach for monitoring
a dialysis treatment by a bioimpedance device in order to correlate
the signals with the progress of the treatment.
[0011] In view of the prior art there is a need for a simple method
that requires only very few fundamental parameters and that
nonetheless provides reliable results on the hydration, nutrition
and training status of a patient at the same time. It is an object
of this invention to provide such a method.
[0012] The problem of the invention is solved by a method according
to claim 1, i.e. by a method to determine at least one of a
mal-hydration component, an adipose tissue component and a lean
tissue component of a patient comprising the steps of determining
chemical or physical properties of the patient and deriving the at
least one component on the basis of the determined chemical or
physical properties of the patient and previously determined values
of a mass or volume fraction of water in lean tissue and a mass or
volume fraction of water in adipose tissue.
[0013] The invention is based on the observation that a model
dividing the body of a patient into a lean tissue compartment, an
adipose tissue compartment and a mal-hydration compartment is
already adequate to minimise the number of parameters involved and
to still provide reliable results. The inventors further recognised
that it is sufficient to establish values for a water volume or
mass fraction for the lean tissue on one hand and for the adipose
tissue on the other hand. To apply the model these fractions can be
taken as fixed values independent of the patient the method is
applied to. According to the concept of the invention it is, apart
from the mal-hydration water compartment, mainly the individual
mixture of these two types of tissues that contributes to the
differential water distribution within the patient so that it is
sufficient to explicitly consider these two types of tissues for
this aspect.
[0014] In the framework of the invention adipose tissue is
considered to consist of fat cells or adipocytes suspended in
extracellular fluid. The adipocytes themselves consist
predominantly of lipids or fat and a small quantity of
intracellular fluid. Adipose tissue should therefore not be
confused with fat even though they are related. Fat is simply the
pure lipid whilst adipose tissue is a mixture of fat and water. The
adipocytes bind a proportion of extracellular fluid which makes up
the total adipose tissue mass. This extracellular fluid is
therefore not free fluid and must be taken into account when
calculating a patient's excess fluid.
[0015] In the prior art two-compartment models have been known that
divide the human body into a fat-free mass and a fat mass
compartment (e.g.: K. J. Ellis, "Human Body Composition: In Vivo
Methods", Physiological Reviews 80, 649 (2000)). In such a model
the fat mass compartment only consists of fat or lipids whereas the
remainder of the body, including the water, is lumped together in
the fat-free mass compartment. This is different to the present
invention that distinguishes between adipose tissue--including a
non-vanishing water component--on one hand and lean tissue on the
other hand. Though the lean tissue compartment is--apart from the
mal-hydration compartment--again defined as the "remainder" of the
body mass, the two tissues are further distinguished by their
different water fractions.
[0016] It is also an object of the invention to provide a device
for a non-invasive, accurate and easy to use body compartment
assessment. The invention therefore also concerns a device
according to claim 9 for carrying out the method according to the
invention, i.e. a device comprising a measurement and/or input unit
configured to provide values for chemical or physical properties of
the patient to be determined, an evaluation unit configured to
derive at least one component of a mal-hydration component, an
adipose tissue component and a lean tissue component on the basis
of the determined chemical or physical properties of the patient
and previously determined values of a mass or volume fraction of
water in lean tissue and a mass or volume fraction of water in
adipose tissue, and a communication link between the measurement
and/or input unit and the evaluation unit.
[0017] In a preferred embodiment the evaluation unit is also
configured to control the measurement and/or input unit for
determining at least one of the chemical or physical properties of
the patient.
[0018] In a further preferred embodiment the evaluation unit is a
microprocessor unit which in turn comprises a microprocessor
program storage unit, wherein in the microprocessor program storage
unit a program for deriving the at least one component on the basis
of the determined chemical or physical properties of the patient
and previously determined values of a mass or volume fraction of
water in lean tissue and a mass or volume fraction of water in
adipose tissue is stored.
[0019] A computer program product according to claim 18 which
comprises a storage medium on which a computer program is stored
which is to be stored in a device according to the invention for
carrying out the method according to the invention where the
evaluation unit comprises a microprocessor storage unit, is also
constituting a part of the invention.
[0020] Various further embodiments of the invention are subject of
the subclaims of the independent claims.
[0021] For an improved understanding of the invention,
non-restrictive examples will be described with reference to the
appended drawings in which
[0022] FIG. 1a shows a schematic illustration of the three
components of the body of a patient representing the mal-hydration
mass M.sub.EX, the lean tissue mass M.sub.LT and the adipose tissue
mass M.sub.AT,
[0023] FIG. 1b shows a schematic illustration of the three
components of a body of a patient according to FIG. 1a (right hand
side) in relation to the mass components as derived by dual x-ray
absorptiometry (DXA) (left hand side),
[0024] FIG. 2 shows a compilation of example values for the various
parameters required in the example embodiments of the invention for
the calculation of the body mass components,
[0025] FIG. 3 schematically shows an embodiment of a device for the
assessment of the body composition of a patient according to the
present invention, and
[0026] FIG. 4 shows a bioimpedance electrode arrangement for whole
body bioimpedance measurements (left hand side) and a bioimpedance
electrode arrangement for segmental body bioimpedance measurements
(right hand side).
[0027] As illustrated in FIG. 1a the body of a patient can be
divided into three components: an excess fluid or mal-hydration
component with mass M.sub.EX, a lean tissue component with mass
M.sub.LT and an adipose tissue component with mass M.sub.AT. For
all three components the extracellular water (ECW) and
intracellular water (ICW) together with other contributions
(minerals, proteins, lipids etc.) are also shown in FIG. 1a. The
excess fluid M.sub.EX which mainly accumulates in the ECV space is
an indicator of the mal-hydration status of a patient. In a healthy
subject M.sub.EX would be vanishing. M.sub.EX may also have a
negative value indicating a hydration status where the patient is
over hydrated.
[0028] The lean and the adipose tissue are distinguished in the
framework of this application by their water contents. The lean
tissue mass M.sub.LT comprises bones, organs (including blood) and
muscles, but no lipids. More sophisticated models could be
considered to include the influence of bone or other tissues, but
for the present purpose such refinements are neglected. Adipose
tissue mass M.sub.AT, on the other hand, is assumed to be largely
comprised of lipids and water in the form of fat cells or
adipocytes.
[0029] According to the concept of the invention it is necessary to
distinguish between the mass fraction .LAMBDA..sub.LT of water in
lean tissue as a first tissue and the corresponding mass fraction
.LAMBDA..sub.AT of water in adipose tissue as a second tissue:
.LAMBDA. LT .ident. D ( ECW LT + ICW LT ) M LT , ( 1 ) .LAMBDA. AT
.ident. D ( ECW AT + ICW AT ) M AT , ( 2 ) ##EQU00001##
wherein D is the density of water (D=0.99823 kg/litre at 36.degree.
C.; for the present purpose a single density value is considered to
be sufficient, however small variations due to solutes in the
different water compartments may be introduced), ECW.sub.LT and
ICW.sub.LT are the volumes of extracellular and intracellular water
in the lean tissue, the latter having the total mass M.sub.LT, and
ECW.sub.AT and ICW.sub.AT are the volumes of extracellular and
intracellular water in the adipose tissue, the latter having the
total mass M.sub.AT. Eqs. (1) and (2) may of course also be written
in terms of fractions per tissue volume, as volume per mass or as
mass per volume without leaving the concept of the invention. It is
only important that the water contribution to the lean tissue on
one hand and to the adipose tissue on the other hand is considered
differently.
[0030] The fractions .LAMBDA..sub.LT and .LAMBDA..sub.AT each have
a contribution .LAMBDA..sub.ECW from the extracellular water and a
contribution .LAMBDA..sub.ICW from the intracellular water:
.LAMBDA. ECW , LT .ident. D ECW LT M LT , ( 3 ) .LAMBDA. ICW , LT
.ident. D ICW LT M LT , ( 4 ) .LAMBDA. E CW , AT .ident. D ECW AT M
AT , ( 5 ) .LAMBDA. I CW , AT .ident. D ICW AT M AT . ( 6 )
##EQU00002##
[0031] According to the concept of the present invention it is
sufficient to previously determine at least values for the mass
fractions .LAMBDA..sub.LT and .LAMBDA..sub.AT. In more refined
embodiments of the invention the mass fractions as defined by some
or all the Eqs. (3) to (6) are used. To determine such values
various experimental methods may be employed. Once these values are
established, as will be shown below, a set of rather simple
equations may be used for routine application that can also be
employed together with less sophisticated experimental methods but
still lead to accurate and reliable results for the masses of the
three body components M.sub.EX, M.sub.LT and M.sub.AT.
[0032] Using dual x-ray absorptiometry (DXA) or dilution
experiments as reference data it is possible to derive the mass
fractions of extracellular and intracellular water independently
for the lean tissue and the adipose tissue mass components. A good
review of such and other methods is given in the aforementioned
article from K. J. Ellis.
[0033] In DXA the attenuation of two x-ray photons having different
photon energies is compared. As a result it is possible to
distinguish between fat mass M.sub.LIPID, lean tissue mass
M.sub.LT,DXA according to DXA and the total bone mineral content
mass M.sub.TBMC of a patient. The relation of these mass components
to the components as used by the invention is shown in FIG. 1b. It
is important to note that the fat mass M.sub.LIPID does only
represent the adipose lipids of the adipose tissue, but not the
adipose water. Furthermore, the lean tissue mass M.sub.LT comprises
parts of the lean tissue mass M.sub.LT,DXA according to DXA and the
total bone mineral content mass M.sub.TBMC. The lean tissue mass
M.sub.LT,DXA according to DXA, on the other hand, also comprises
the mal-hydration mass M.sub.EX and the adipose water mass.
[0034] With the help of dilution experiments as a further reference
method certain compartments of a body can be probed by selecting
appropriate tracer substances that dilute just in the chosen
compartment. Typical examples are the ECW, ICW or the total body
water (TBW) volumes.
[0035] Taking the reference data from such experiments the mass
fractions of Eqs. (1) to (6) can be derived by optimisation and
also by analytical methods in an effort to map the observed data as
closely as possible for as many individuals as possible. An example
result of such a procedure is compiled in FIG. 2.
[0036] Once at least one of the water mass fractions
.LAMBDA..sub.LT, .LAMBDA..sub.ECW,LT or .LAMBDA..sub.ICW,LT of the
lean tissue mass component and at least one of the water mass
fractions .LAMBDA..sub.AT, .LAMBDA..sub.ECW,AT or
.LAMBDA..sub.ICW,AT of the adipose tissue mass component have been
previously determined it is now possible to derive vice versa at
least one of the masses of the mal-hydration mass M.sub.EX, the
lean tissue mass M.sub.LT and the adipose tissue mass M.sub.AT from
routine experimental measurement data of chemical or physical
properties of the patient without having to use all the
experimental methods that were applied to obtain the reference
data. Depending on the kind of chemical or physical properties that
are to be determined by the routine measurements, various modes of
the invention are possible. Before an exemplary device according to
the invention will be explained in detail five examples for such
methods according to the invention are described:
EXAMPLE 1
[0037] Chemical or physical properties of the patient to be
determined:
ECW: volume of the total extracellular water of the patient, ICW:
volume of the total intracellular water of the patient, M: whole
body mass of the patient.
[0038] Each of these properties can be split into contributions
from the three components:
ECW=ECW.sub.EX+ECW.sub.LT+ECW.sub.AT (7),
ICW=ICW.sub.LT+ICW.sub.AT (8),
M=M.sub.LT+M.sub.AT+M.sub.EX (9).
[0039] Using Eqs. (3) to (6), Eqs. (7) to (9) can be solved for the
masses of all three components:
M EX = D ECW - M ( .LAMBDA. ECW , AT k 1 .LAMBDA. ICW , AT ) + k 1
D ICW ( 1 - .LAMBDA. ECW , AT - k 1 .LAMBDA. ICW , AT ) wherein (
10 ) k 1 = .LAMBDA. ECW , AT - .LAMBDA. ECW , LT .LAMBDA. ICW , LT
- .LAMBDA. ICW , AT , ( 11 ) M LT = D ICW - ( M - M EX ) .LAMBDA.
ICW , AT ( .LAMBDA. ICW , LT - .LAMBDA. ICW , AT ) and ( 12 ) M AT
= M - M LT - M EX . ( 13 ) ##EQU00003##
EXAMPLE 2
[0040] Chemical or physical properties of the patient to be
determined:
TBW: volume of the total body water of the patient M.sub.TBMC: mass
of total bone mineral content of the patient M: whole body mass of
the patient.
[0041] The total body water TBW can be split into three parts
originating from the three components:
TBW = 1 D ( .LAMBDA. LT M LT + .LAMBDA. AT M AT + M EX ) . ( 14 )
##EQU00004##
[0042] The lean tissue mass M.sub.LT is split in this example into
its water fraction and a rest fraction M.sub.Min+Pro mainly
attributing for minerals and proteins:
M.sub.LT=.LAMBDA..sub.LTM.sub.LT+M.sub.Min+Pro (15).
[0043] Taking k.sub.TBMC to be the share of the total bone mineral
content mass M.sub.TBMC of M.sub.Min+Pro one has:
M.sub.TBMC=k.sub.TBMCM.sub.Min+Pro (16)
wherein a typical value of k.sub.TBMC is 0.2074. Together with the
mass balance Eq. (9) the set of Eqs. (14) to (16) can be solved for
the three component masses:
M EX = D TBW - M TBMC k TBMC ( 1 - .LAMBDA. AT ) ( .LAMBDA. LT -
.LAMBDA. AT ) - .LAMBDA. AT M ( 1 - .LAMBDA. AT ) ( 17 ) M LT = M
TBMC k TBMC ( 1 - .LAMBDA. LT ) ( 18 ) ##EQU00005##
and M.sub.AT is obtained by using Eq. (13).
EXAMPLE 3
[0044] Chemical or physical properties of the patient to be
determined:
TBW: volume of the total body water of the patient M.sub.LIPID:
lipid mass of the patient M: whole body mass of the patient.
[0045] The mass of mal-hydration water can be expressed as
M.sub.EX=D(TBW-TW.sub.LT-TW.sub.AT) (19),
wherein TW.sub.LT is the sum of the extra- and intracellular water
volumes in the lean tissue and TW.sub.AT is the sum of the extra-
and intracellular water volumes in the adipose tissue. The lipid
mass M.sub.LIPID of the patient is the mass M.sub.AT of the adipose
tissue without the water mass in the adipose tissue:
M.sub.LIPID=M.sub.AT-DTW.sub.AT=M.sub.AT(1-.LAMBDA..sub.AT)
(20).
[0046] Inserting Eqs. (13) and (20) in Eq. (19) by making use of
Eqs. (1) and (2) and solving for the mal-hydration water mass
M.sub.EX one obtains:
M EX = D TBW - .LAMBDA. LT M + M LIPID 1 - .LAMBDA. AT ( .LAMBDA.
LT - .LAMBDA. AT ) ( 1 - .LAMBDA. LT ) ( 21 ) ##EQU00006##
[0047] M.sub.AT may be calculated by solving Eq. (20) and M.sub.LT
by solving Eq. (9):
M AT = M LIPID ( 1 - .LAMBDA. AT ) and ( 22 ) M LT = M - M AT - M
EX . ( 23 ) ##EQU00007##
EXAMPLE 4
[0048] Chemical or physical properties of the patient to be
determined:
ECW: volume of the total extracellular water of the patient
M.sub.LIPID: lipid mass of the patient M: whole body mass of the
patient.
[0049] The mass of mal-hydration water can be expressed as
M.sub.EX=D(ECW-ECW.sub.LT-ECW.sub.AT) (24),
wherein the parameters are as defined in Example 1. Inserting Eqs.
(13) and (22) in Eq. (24) by making use of Eqs. (2), (3) and (5)
and solving for the mal-hydration water mass M.sub.EX one
obtains:
M EX = D ECW - .LAMBDA. ECW , LT M + M LIPID 1 - .LAMBDA. AT (
.LAMBDA. ECW , LT - .LAMBDA. ECW , AT ) ( 1 - .LAMBDA. ECW , LT ) (
25 ) ##EQU00008##
M.sub.AT and M.sub.LT may be derived similar as in Example 3, i.e.
according to Eqs. (22) and (23).
EXAMPLE 5
[0050] Chemical or physical properties of the patient to be
determined:
ECW: volume of the total extracellular water of the patient ICV:
volume of the total intracellular cells of the patient M: whole
body mass of the patient.
[0051] This example has similarities with Example 1. However,
instead of the ICW the intracellular volume ICV as a whole,
including the volume of matter not being water is determined. In
this case it is useful to introduce further constants that are
related to the water mass fractions as defined by Eqs. (3) to
(6).
[0052] In analogy to the ICW the total ICV can be split into
components ICV.sub.AT for the adipose tissue and ICV.sub.LT for the
lean tissue. These are linked to the masses M.sub.LT of the lean
tissue component and M.sub.AT of the adipose tissue component by
proportionality constants .zeta..sub.LT and .zeta..sub.AT (example
values as taken from the international patent application
PCT/EP2004/007023 are .zeta..sub.LT=0.620 litres/kg and
.zeta..sub.AT=0.987 litres/kg):
ICV=ICV.sub.LT+ICV.sub.AT=M.sub.LT.zeta..sub.LT+M.sub.AT.zeta..sub.AT
(26).
[0053] Substituting M.sub.AT in Eq. (26) with the help of Eq. (9)
and solving the resultant equation for M.sub.LT, Eq. (27) is
obtained:
M LT = ICV - .zeta. AT ( M - M EX ) .zeta. LT - .zeta. AT . ( 27 )
##EQU00009##
[0054] Before the lean tissue mass M.sub.LT can be derived, the
mal-hydration mass M.sub.EX has to be calculated. The starting
point is again the observation that this component manifests itself
entirely in the ECV space, i.e. the mal-hydration water volume can
be derived as ECW.sub.EX by solving Eq. (7).
[0055] Using the following definitions for the volume of
extracellular water per unit mass of lean tissue
.lamda..sub.ECW,LT,
.lamda. ECW , LT .ident. ECW LT M LT = .LAMBDA. ECW , LT D ( 28 )
##EQU00010##
and for the volume of extracellular water per unit mass of adipose
tissue .zeta..sub.ECW,AT,
.lamda. ECW , AT .ident. ECW AT M AT = .LAMBDA. ECW , AT D , ( 29 )
##EQU00011##
and further introducing the definition
A .ident. .lamda. ECW , LT - .lamda. ECW , AT .zeta. LT - .zeta. AT
, ( 30 ) ##EQU00012##
[0056] Eq. (7) can be solved with the help of Eqs. (9) and
(27):
ECW EX = ECW - A ICV + ( A .zeta. AT - .lamda. ECW , AT ) M ( 1 + (
A .zeta. AT - .lamda. ECW , AT ) D ECW ) ( 31 ) ##EQU00013##
wherein D.sub.ECW is the density of the extracellular water
(=0.99823 kg/litre). Once the mal-hydration volume ECW.sub.EX has
been determined (and thus the mal-hydration mass M.sub.EX), the
lean tissue mass M.sub.LT can be calculated from Eq. (27) and the
adipose tissue mass M.sub.AT by Eq. (13).
[0057] As can be seen from all five examples, the chemical or
physical properties that have to be determined of the patient may
vary from one example to another. It is yet in all examples
possible to determine at least one of a mal-hydration component, an
adipose tissue component and a lean tissue component of the patient
on the basis of the determined chemical or physical properties and
previously determined values of a mass or volume fraction of water
in lean tissue and a mass or volume fraction of water in adipose
tissue. The general concept of the present invention is therefore
not limited to specific methods where specific properties of a
patient have to be determined. The key element of the invention to
derive the at least one body component is to make appropriate use
of the previous determined values of a mass or volume fraction of
water in lean tissue and a mass or volume fraction of water in
adipose tissue. The same applies not just to the method but also to
any device according to the invention.
[0058] The method according to Example 1 is now used to describe an
embodiment of a device according to the invention in detail (FIG.
3). The device 10 comprises an evaluation unit that consists of a
microprocessor unit 1 which in turn comprises a microprocessor
program storage unit 1a. By means of a communication link 4 the
microprocessor unit 1 is connected to an interface unit 2 and a
computer storage unit 3. A program for determining the masses
M.sub.EX, M.sub.LT and/or M.sub.AT of a patient is stored in the
microprocessor program storage unit 1a. This program may have been
transferred beforehand to the microprocessor program storage unit
1a from a computer program product like a floppy disk, a CD-ROM, a
DVD, a memory stick, a server or any other suitable storage medium
on which the program was stored. In this case the device 10
comprises the necessary interface circuitry (not shown) whose
design is--dependent of the type of computer program
product--obvious to a person skilled in the art.
[0059] The microprocessor program controls the device to determine
patient impedance values for two or more frequencies. For the
corresponding measurement the device 10 comprises a bioimpedance
measurement means 5 which is connected to the interface unit 2 by a
communication link 6. The bioimpedance measurement means 5 can be
capable of automatically compensating for influences on the
impedance data like contact resistances. An example for such a
bioimpedance measurement means 5 is a device from Xitron
Technologies distributed under the trademark Hydra.TM. and also
described in WO 92/19153.
[0060] For the bioimpedance measurement various electrode
arrangements are possible. In FIG. 3 only two electrode elements 5a
and 5b are attached to the bioimpedance measurement device 5. Each
of the electrode units 5a and 5b consists of a current injection
electrode and a potential pick-up electrode (not shown). By
applying the two electrode units 5a and 5b to the wrist and the
ankle of a patient, respectively, as outlined in the left part of
FIG. 4, the whole body impedance may be determined. Under this
electrode configuration the body may be regarded as a combination
of several homogenous cylinders, representing trunk, legs and arms.
Average contributions of these components to the total impedance
are also provided in FIG. 4, mainly resulting from the differing
cross-sections of the cylinders.
[0061] By using additional electrodes on shoulder and hip, these
cylindrical segments may be measured separately, thereby possibly
increasing the accuracy of volume determinations. Such a
configuration is displayed on the right hand side of FIG. 4.
Additional electrode units 5a' and 5b' are attached close to the
shoulder and the hip of the patient enabling a segmental approach
to the body elements leg, arm and trunk.
[0062] The program stored in the microprocessor storage unit 1a
initiates an impedance measurement at least two given frequencies
and records the corresponding current and voltage signals, both
being below critical thresholds so that the device just
non-invasively probes the patient impedance without having any
impact on the patient at all. The device can easily be applied by
the patient him- or herself without necessarily requiring medical
staff.
[0063] Returning to the embodiment shown in FIG. 3, the weight or
whole body mass M of the patient can be entered into the device 10
via any input unit (not explicitly shown) connected to or being
part of the interface unit 2 (e.g. a keyboard, touch screen etc.).
This may be assisted by a weighing means 7 linked to the interface
unit 2 by a communication link 8.
[0064] In the embodiment shown in FIG. 3 the interface unit 2
serves as an interface by which the values of the whole body mass M
and any measured impedance or applied current and voltage values
are directly exchanged via the communication link 4 between the
computer storage unit 3, the program stored in the microprocessor
program storage unit 1a, the interface 2 and the bioimpedance
measurement means 5. As indicated it is also possible that any data
from or to the weighing means 7 are directly transferred between
the connected components via the communication links.
[0065] The program stored in the microprocessor storage unit 1a is
now--with the help of stored previously established
data--processing the stored data in order to determine any
contributions of various body tissues components to the whole body
mass M.
[0066] As outlined above the ECW is determined by exploiting the
fact that the electrical impedance of body tissue changes when
alternating currents of different frequencies are applied to the
patient via the electrodes. At low frequencies the cell membranes
behave as insulators and the applied current passes only through
the ECV spaces, i.e. the ECW volume. At high frequencies the cell
membranes become more conductive and thus current passes through
both the ICV and ECV spaces. Measurement of the impedance over at
least two frequencies, better over a range of frequencies, allows
the determination of both the ECW and the ICW. In the prior art as
described above such methods have been disclosed. A more refined
model was developed recently by the same inventors as of the
present invention in the patent application PCT/EP2004/007023 whose
disclosure is hereby explicitly enclosed in the current application
by reference.
[0067] Once any values for the ECW, ICW and whole body mass M as
chemical or physical properties of the patient have been determined
the microprocessor program applies Eqs. (10) to (13) to receive
values for at least one of a mal-hydration component, a adipose
tissue component and a lean tissue component, here the masses
M.sub.EX, M.sub.LT and M.sub.AT of all three components, on the
basis of previously determined values of a mass or volume fraction
of water in lean tissue and a mass or volume fraction of water in
adipose tissue.
[0068] The results are finally completely or partially passed on to
an output unit 9 which typically is a display device which displays
the results to a user. Further results--independent whether as an
intermediate or as an additional result--might add to the
informative character of the display.
[0069] The compartmental results may be stored in the device to
enable a trend analysis including previously derived results. It
has also proved useful to smooth the data by deriving weighted
average values from the latest and the previous data. For this
purpose various algorithms are available in the art to reduce
statistical scatter in the data. A useful improvement in the
averaging procedure for the current result to be displayed was
obtained by giving the latest measurement the highest weight and by
decreasing the weight of other, previous measurements with
increasing time that has passed since the measurements were
taken.
[0070] The disclosed device and method according to the invention
are hence able to provide for a powerful and more accurate
technique for the management of the hydration status of a patient.
In case the weight M.sub.AT of the adipose tissue component and/or
the weight M.sub.LT of the lean tissue component are also
determined the invention is yielding useful further results which
allow conclusions about the nutrition and/or training status of the
patient. This is not dependent on whether the patient is really
mal-hydrated or not.
[0071] It is important to note that the concept of the invention is
not limited to the use of a bioimpedance measurement means on one
hand and on the application of Example 1 on the other hand. For
applying the concept of Example 1 it is not relevant as to how the
values of the properties of the patient have been determined. In
particular Examples 2, 3 and 4 provide examples of such variations
of the concept of the invention. Instead of bioimpedance other
techniques may be applied that are suitable to reveal the separate
character of the lean tissue on one hand and the adipose tissue on
the other hand. As example technique to determine the lipid mass
M.sub.LIPID or the total bone mineral content mass M.sub.TBMC DXA
measurements are recalled. Total body water, ICW or ECW may also be
derived by dilution methods.
[0072] In the simplest embodiment of a device according to the
invention such a device comprises an input unit by which such
chemical or physical property values may be entered into the
device. As described above such a device may also comprise at least
partly the measurement means to determine the chemical or physical
properties of the patient. In such a case it is possible that the
evaluation unit also controls the measurement unit for carrying out
the measurement of the chemical or physical properties of the
patient in an automated manner.
[0073] Hence management of any individual is possible, independent
of any treatment modality. The invention is particularly applicable
for patients which undergo end stage renal failure treatments like
hemodialysis, hemofiltration, hemodiafiltration or any forms of
peritoneal dialysis (all these treatment modalities are summarised
throughout this patent application by the terminology "a dialysis
treatment"). A characterisation of hydration status might also be
highly desirable within the intensive care setting, since highly
abnormal electrolyte- and fluid conditions are frequent for such
patients. Furthermore, measurement in virtually any setting where
nutrition or fitness parameters are required, including home,
pharmacies, medical practices, dialysis units, wards, fitness
centres, etc., would be practical.
* * * * *