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Clinical Science (1982) 63,375s-377s
Index for normalization of blood volume
N G U Y E N P H . C H A U , ' R O B E R T C . T A R A Z I , 2 F E T N A T M. F O U A D , *
M I C H E L E. S A F A R , 3 W I L L E M H . B I R K E N H i i G E R 4 A N D
P E T E R W. DE L E E U W '
UER de saint Quentin, UniversitP & Picardie, France, 2Cleveland Clinic Foundation, Cleveland, OH, U S A . .
'Haemodynamics Laboratory, Broussais Hospital, Paris, France, and 'Zuiderziekenhuis, Rotterdam, The Netherlands
Summary
Introduction
1. A general method for the development of a
blood volume index was devised to allow interindividual comparisons.
2. An accurate and acceptable blood volume
index had to fulfil certain criteria; it had to be (1)
not correlated with body size, (2) highly correlated with blood volume, (3) either dimensionless or expressible in units of length or of surface
area and (4) simple to calculate.
3. Available data, from the Broussais Hospital, Paris, the Zuiderziekenhuis, Rotterdam and
the Cleveland Clinic, Cleveland, Ohio, included
six groups of normal subjects, male essential
hypertensive patients and female essential hypertensive patients.
4. Extensive calculations, based on the available data, indicated that the equation BVI =
B V / ( U ~ HW)
. (BVI = blood volume index, BV
= blood volume, H = body height, W = body
weight and a = a constant depending on the
chosen units) was the simplest index which
satisfied the above requirements.
5. As the equation SA = 0.165 d ( H . W) (SA
= body surface area, in m2, H in m and Win kg)
is almost identical with the Dubois 8~ Dubois
formula predicting body surface area from height
and weight, one may choose a = 0.165 and the
index BVI = BV/[O. 165
W)l ( H in m, Win
kg, BV in ml and BVI in ml/m2). Thus blood
volume is referred to body surface area.
6. Blood volume referred to unit body surface
area appears, at the present, to be the most
appropriate 'blood volume index'. However,
studies of data from larger groups and from more
centres are needed to confirm this conclusion.
Key words: blood volume index.
Correspondence: Dr Nguyen Phong Chau, Universite de Picardie, Unite d' Engseignement et de
Recherche, Service de Mathematiques, 48 rue
Raspail, 02100 St Quentin, France.
Systemic blood flow and fluid volumes are highly
correlated with body sue. A comparison study of
volume or flow values must take account of
interindividual differences in body size. Volume
values are usually referred to unit body height
(H), unit body weight (W)or unit body surface
area (SA). There is as yet no universal agreement
regarding the best index for expressing these
values. The resulting divergence of normalization
procedures adds to the difficulties in comparing
data from different investigators. It was thought
desirable therefore to define a general method to
construct volume and flow reference indices.
Since any acceptable index must be applicable
to data from different laboratories, this study
involved three different centres.
The present report, part of which was presented to the ISH Committee for Reference Indices,
is a preliminary communication in which only
blood volume data were analysed.
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Methods
Theoretical
Blood volume must be referred to body s u e
because it is highly correlated with body size. As
a result, any developed volume index must be
independent of body size. This condition,
however, is not sufficient per se to define an
adequate volume index. Among other requisites,
one must also be guided by criteria of simplicity.
In order to satisfy both mathematical and clinical
considerations, we proposed four requisites for a
blood volume index (BVI). BVI had to be:
1. Not correlated with body height (H) and
body weight ( W).
2. As closely correlated as possible with the
actual blood volume.
N. Ph. Chau et al.
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3. Either dimensionless or expressible in units
of length or of surface area.
4. Simple to calculate.
As a simple function of volume, height and
weight, we suggested the formula
In total, six groups of subjects were available for
the study (Table 1).
For each subject group and for each dimension
of BVI (= Lo, L' or L2) the correlation
coefficients between blood volume index and
either height or weight were calculated. The
values of a and /3 that define the non-significant
correlation (P > 0.10) between BVI and H or W
were identified.
Calculations showed that no index of dimension Lo or L2 met with the first requisite in the six
groups of subjects. In particular, the indices
BVIH and BV/ W proved unacceptable. With an
index of dimension L', the simplest aand pvalues
for which BVI was not correlated with H and W
in the six groups of subjects were a = 0-5 and /3 =
0.5. In that case,
BVI = BV/(aH". WP)
(1)
( a > 0, p > 0 and a, a constant depending on the
chosen units). Equation (1) generalizes the
classical indices BV, (=BV/H), BV, (=BV/S)
and BV, (=BV/W). Assuming dimension W =
L3 ( L = length), the eqn. (2) gives the dimension
of BVI:
dim. BVI = L3-a-3P
(2)
Experimental
Data for this study were derived from three
centres: the Broussais Hospital, Paris, the
Zuiderziekenhuis, Rotterdam and the Cleveland
Clinic. The subjects studied were either normal
controls or male and female patients with
essential hypertension. Weight and height were
measured for subjects without shoes and outer
clothes. Blood volume was estimated by '"I or
1251 radio-iodinated human serum albumin.
Details of methodology in each centre have been
published [l-31; however, many of the results
analysed were derived from data not reported
previously.
BVI = BV/[a d ( H . W)l
(3)
The term d(H.W) is closely related to body
surface area (SA) as predicted from height and
weight by the Dubois & Dubois formula [41.
SA = 0.007184 H'J.725WO.425
(m2)
(cm) (kg)
(4)
SA = 0 . 1 6 5 d ( H . W)
(5)
In fact,
(SA in m2,H in m and Win kg) predicts almost
the same SA as eqn. (4) (with less than 4% of
relative errors in all subjects).
By using a = 0.165 (see eqn. 3), the formula
Results
The Paris data included a group of normal male
subjects and a group of male essential hypertensive patients. The Rotterdam data included
two groups, one female and the other male
essential hypertensive patients. The Cleveland
data included a group of female and a group of
male subjects, each including both normotensive
subjects and patients with essential hypertension.
BVI = BV/[O*065
d(H.W)l
(6)
(BV in ml, H in m, Win kg and BVI in ml/m2)
gives the simplest volume index in our subjects
which satisfies the prerequisites and can be
interpreted as a reference of volume to body
surface area.
TAHI.I<
I. Characteristics of the six groups of subjects: blood volume. volume index (eqn. 6 ) and their correlation with body size
Data are from M.E.Safar (groups I and 2), P. W. de Leeuw and W. H. Birkenhager (groups 3 and 4). and F. M. Fouad
and R. C. Tarazi (groups 5 and 6). Means SEM are shown. N = Normal controls; H = essential hypertensive: M = male:
F = female; n = number of subjects; H = height; W = weight; BV = blood volume: BVI = blood volume index (eqn. 6):
* P < 0.001; t a residual correlation was observed in this group (0.01 < P < 0.05).
Group
Subjects
Sex
n
Age
(years)
H
(cm)
W
(kg)
Blood
volume
(ml)
Correlationcoefficient
BY-H
BV-W
BVI-H
BVI-W
BVI-BV
Normalization of blood volume
Discussion
As blood volume is highly correlated with both
height and weight, any blood volume index must
be independent of these factors. Our data showed
that the indices BVIH and, in particular, BVI W,
which is widely used, did not satisfy this requisite.
The data indicated that blood volume should be
referred to the geometric mean of height and
weight I= d ( H . W ) ] . As the term d ( H . W )
closely resembles the Dubois & Dubois formula
(eqn. 4), predicting surface area on the basis of
height and weight, an attempt was made to relate
W) to surface area. It was found that eqn.
(5) predicts almost the same surface area as the
Dubois & Dubois formula. As a result, eqn. 6 was
suggested. Reference of blood volume to surface
area (eqn. 6) appears, at the present, to be the
most appropriate index. However, data from
larger groups and from more centres are needed
to test this conclusion.
d(H.
Acknowledgments
This work was made possible by a generous
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support from E. R. Squibb (Princeton, N.J.) as
well as by a grant from the Laboratories
SPECIA (to N.P.C.). The work at the Cleveland
Clinic Foundation was supported in part by
Grant HL-6835 from the National Heart, Lung
and Blood Institute. ISH Committee for
Reference Indices: R. C. Tarazi, chairman, W. H.
Birkenhager, N. P. Chau, H. P.Dustan, S.Julius,
P. I. Korner and M.E. Safar.
References
111 SAFAR, M.E., CHAU,N.P.,WEISS, Y.A., SIMON,A C H . &
MILLIE& P.L. (1976) The pressurevolume relationship in
normotensive and essential hypertensive patients. Clinical
Science, SO, 207-212.
121 DE LEEUW,P.W.,KHO, T.L., FAME, H.E., BIRKENHAGER,
W.H. & Wesmn, A. (1978) Haemodynamic and endocrinological profiles in essential hypertension. Acta Medica
Scandinauica, Suppl. 622, 1-86.
I31 TARAZI,R.C. (1976) Hemodynamic role of extracellular fluid in
hypertension. Circulation Research, 38 (Suppl. II), 11-73-11-81.
141 DUBOIS,D. & DIJBOIS,
E.F. (1916) Clinical calorimmy. X. A
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