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Eur J Pediatr (2010) 169:883886

DOI 10.1007/s00431-010-1140-8

ORIGINAL PAPER

Plasma water as a diagnostic tool in the assessment


of dehydration in children with acute gastroenteritis
Annemarie Plaisier & Femke Maingay-de Groof & Roechama Mast-Harwig &
Patricia M. J. Kalkman & Remi W. Wulkan & Renee Verwers & Marjolein Neele &
Wim C. J. Hop & Michael Groeneweg

Received: 12 November 2009 / Accepted: 5 January 2010 / Published online: 2 February 2010
# Springer-Verlag 2010

Abstract Acute gastroenteritis is common in childhood.


The estimation of the degree of dehydration is essential
for management of acute gastroenteritis. Plasma water
was assessed as a diagnostic tool in children with acute
gastroenteritis and dehydration admitted to hospital. In a
prospective cohort study, 101 patients presenting at the
emergency department with dehydration were included.
Clinical assessment, routine laboratory tests, and plasma
water measurement were performed. Plasma water was
measured as a percentage of water content using dry
weight method. During admission, patients were rehydrated in 12 h. Weight gain at the end of the rehydration
period and 2 weeks thereafter was used to determine the
percentage of weight loss as a gold standard for the
severity of dehydration. Clinical assessment of dehydration was not significantly associated with the percentage
of weight loss. Blood urea nitrogen (r=0.3, p=0.03),
base excess (r=0.31, p=0.03), and serum bicarbonate
(r=0.32, p=0.02) were significantly correlated with the
percentage of weight loss. Plasma water did not correlate
with the percentage of weight loss. On the basis of the
presented data, plasma water should not be used as a
A. Plaisier : F. Maingay-de Groof : R. Mast-Harwig :
P. M. J. Kalkman : M. Groeneweg (*)
Department of Pediatrics, Maasstad Hospital,
P.O. Box 9100, 3075 EA Rotterdam, The Netherlands
e-mail: groenewegm@maasstadziekenhuis.nl
R. W. Wulkan : R. Verwers : M. Neele
Department of Clinical Chemistry, Maasstad Hospital,
Rotterdam, The Netherlands
W. C. J. Hop
Department of Biostatistics, Erasmus Medical Centre,
Rotterdam, The Netherlands

diagnostic tool in the assessment of dehydration in


children with acute gastroenteritis.
Keywords Plasma water . Dehydration . Diagnosis .
Gastroenteritis . Children

Introduction
Dehydration is the most important complication of acute
gastroenteritis, and it is the major reason for hospital
admission [6, 14].
The golden standard for the assessment of the severity of
dehydration is the percentage loss in body weight [1, 5, 6,
10, 14, 15], as measured by the difference between weight
on admission and at 2 weeks after discharge, divided by
weight at 2 weeks after discharge. Several clinical scores
have been developed [5, 10]. According to the clinical
score of the American Academy of Pediatrics (AAP) [1],
patients are classified into three subgroups: mild dehydration (35%), moderate dehydration (69%), and severe
dehydration (>10%) [1, 6]. Clinical scores for dehydration
tend to underestimate the severity of dehydration and show
only moderate agreement between observers [6, 15].
It is recommended to perform laboratory tests in
dehydrated children if intravenous rehydration therapy is
started, if there are signs and symptoms of increased serum
sodium and in circulatory shock [6, 12]. Variables that are
correlated best with the percentage of weight loss are:
bicarbonate, blood urea nitrogen, and low pH in combination with a high base excess [3, 6, 9, 10, 14, 15]. However,
none of the laboratory tests studied and presented in
literature today can accurately estimate the percentage of
weight loss in a general pediatric practice [12].

884

In dehydration, the percentage of weight loss was


directly associated with the percentage of plasma volume
lost [4, 13]. It was, therefore, hypothesized that plasma
water may reflect the severity of dehydration. In 1952,
Katcher et al. [4] studied plasma water in infants with
dehydration. Plasma water was low in dehydrated children
but recovered soon after rehydration [7].
In this study, we evaluated plasma water as a diagnostic
tool in the assessment of dehydration in children with acute
gastroenteritis admitted to hospital with moderate to severe
dehydration.

Methods
The study was approved by the Medical Ethics Committee
of the Maasstad Hospital Rotterdam. Between March 2006
and June 2008, all patients with acute gastroenteritis and
dehydration visiting the Emergency Department of the
Maasstad Hospital Rotterdam were asked to participate in
the study. Exclusion criteria were: underlying metabolic
disorders (e.g., diabetes mellitus), diabetes insipidus, and
renal disease. Severity of dehydration was estimated on the
basis of clinical assessment according to the practice
parameter of the AAP [1], consisting of the following
variables: blood pressure, quality of pulses, heart rate, skin
turgor, depth of fontanel, humidity of mucous membranes,
depth of eyes, capillary refill time, mental status, urine
output, and thirst. Total scores consisted of sum of all
variables ranging from one to three per variable. Plasma
water was determined using a dry weight method (Sartorius Technologies B.V. Eindhoven, the Netherlands). The
measurement takes 50 L of heparin plasma and is
completed in 3 min. The plasma was evaporated to dryness
(constant weight) by infrared radiation. Before and during
evaporation, the sample weight was measured by automated
weighing. The percentage of initial water content was then
calculated from the wet and dry weight. From every blood
sample, the plasma water was calculated twice (duplo
measurements). The coefficient of variation calculated from
50 measurements in duplicate is 0.5%. The following
laboratory tests were performed: sodium, potassium, chloride, blood urea nitrogen (BUN), creatinine, and venous
blood gas analysis.
After clinical assessment of the severity of dehydration,
all patients were rehydrated in 12 h. Patients were weighed
before treatment, after 12-h rehydration and daily until
discharge and 2 weeks after discharge at the outpatient
clinic of the Maasstad Hospital Rotterdam. The golden
standard for dehydration was based on weight gain after
rehydration (difference between weight on admission and at
2 weeks after discharge divided by weight at 2 weeks after
discharge). Results of plasma water measurements in

Eur J Pediatr (2010) 169:883886

dehydrated patients were compared to plasma water


measurements of healthy controls (n=12), visiting the
outpatient clinic for functional disorders.

Statistical analysis
Two-tailed Wilcoxon rank-sum test was used to test clinical
variables (mental status, quality of pulses, quality of breathing, skin turgor, fontanel, mucous membranes, eyes, extremities, urine output, thirst, capillary refill time) with the
percentage of weight loss (data not shown). Associations
between continuous variables (all laboratory tests, including:
plasma water, sodium, potassium, chloride, BUN, serum
creatinine, and venous blood gas analysis) are investigated
using Spearman correlation coefficients. P=0.05 (two-sided)
was considered the limit of significance.

Results
One hundred one patients (46 girls) were included in the
study between March 2006 and June 2008. Demographic
data of all 101 patients are listed in Table 1. Fifty-eight
of patients were younger than 2 years of age, 32 were 2
5 years old, and 11 patients were older than 5 years. For
32 children, the percentage of weight loss could not be
determined because of missing data. Demographic data of
these 32 children did not differ from the total group (data
not shown). According to the percentage of weight loss,
13/69 patients were slightly dehydrated (less than 3%), 18/
69 were mildly dehydrated (35%), 12/69 moderately

Table 1 Demographics and


clinical characteristics

Total (n=101)

Parameter

Sex
Boy
Girl

55
46

Age
<2 years
58
25 years
32
512 years
11
Percentage of weight loss
<3%
13
35%
18
69%
12
9%
25
Not evaluable
33
Duration of admission
Median
3 days
Range
110 days

Eur J Pediatr (2010) 169:883886

885

-5

-10

-15

-20

p<0.02
-10,0

0,0

10,0

20,0

Percentage of weight loss

Blood urea nitrogen (mmol/l)

25,0

20,0

15,0

10,0

Discussion

5,0

0,0

p<0.02
-10,0

0,0

10,0

20,0

Percentage of weight loss

25

Bicarbonate (mmol/l)

dehydrated (69%), and 26/69 severely dehydrated (more


than 9%).
The median duration of admission was 3 days (range 1
10 days; Table 1). Duplo measurements of plasma water
showed good reproducibility with an intraclass correlation
of 0.95 (data not shown).
A decreased level of consciousnesses was significantly
correlated with the percentage of weight loss (p<0.05, twotailed Wilcoxon rank-sum test). All other clinical signs did
not significantly correlate with the percentage of weight
loss (data not shown). Blood urea nitrogen (r=0.3, p=0.03,
spearman correlation), base excess (r=0.31, p=0.03), and
serum bicarbonate (r=0.32, p=0.02; Fig. 1) significantly
correlated with the severity of dehydration.
Plasma water did not significantly correlate with the
percentage of weight loss (r=0.21, p=0.98). In addition, no
difference in plasma water levels was found between
patients and healthy controls (Fig. 2).
Subgroup analysis showed that there was a trend towards
a higher percentage of plasma water in moderate to severe
dehydration (>6% weight loss).

This is the first study in which plasma was measured in a


large group of children with acute gastroenteritis and
dehydration.
This study shows that clinical assessment of dehydration
does not reflect the percentage of weight loss and that urea
nitrogen, bicarbonate, and base excess are significantly
correlated with the percentage of weight loss. These
findings are in accordance with studies by others [3, 6, 9,
10, 12, 14, 15].

20

96
15

10

p<0.02
-10,0

0,0

10,0

20,0

Plasma water (%)

Base Excess (mmol/l)

94

mean of controls
+1 SD
mean of controls

92

mean of controls
-1 SD

Percentage of weight loss

Fig. 1 Spearman correlation of percentage of weight loss with base


excess (0.31 ; p=0.03), blood urea nitrogen (0.3; p=0.03), and serum
bicarbonate (0.32; p=0.02)

90

-10,0

0,0

10,0

20,0

Percentage of weight loss

Fig. 2 Correlation of plasma water and percentage of weight loss

886

Plasma water was not correlated with the percentage of


weight loss. Subgroup analysis showed that there was a
trend towards a higher percentage of plasma water in
moderate to severe dehydration (>6% weight loss).
How can we explain our findings on plasma water?
It is evident that plasma water is not a reliable measure
to assess hydration status of children with acute gastroenteritis and dehydration. The physiological regulation of
total body water and plasma water is complex and dynamic.
Fluid balance is influenced by renal responses (e.g.,
arginine vasopressin) and by responses to vascular tonicity
(e.g., aldosterone). It is evident from studies in experimental animals and in healthy humans that it takes some time
for this complex regulatory system to find an equilibrium
[2]. Hydration status can alter quickly in a response to rapid
intake of a hypotonic fluid (e.g., water), and renal responses
will protect against fluid overload (by producing hypoosmolar urine). In addition, the body will respond to
alterations in plasma osmolality. If initial fluid loss also
results in electrolyte loss (like in acute gastroenteritis), the
increase in plasma osmolality will be only moderate, which
results in an attenuated mobilization of intracellular fluid to
the plasma. Plasma water will increase more slowly
accordingly. In addition, in a state of dehydration, rapid
oral fluid intake can lead to rapid increase plasma water,
before intracellular rehydration has started. We measured
plasma water at one moment in time in children with acute
gastroenteritis and dehydration, and probably none of these
childrens fluid status was fully balanced. We, therefore,
hypothesize that plasma water differs from child to child
dependent of the actual fluid balance they are in the
moment blood is drawn to measure plasma water. Factors
like oral fluid and electrolyte intake, the amount of ongoing
fluidand electrolyte losses and differences in body size
and compositionmay have greatly influenced our results
[2, 11].
Subgroup analysis showed that there was a trend towards
a higher percentage of plasma water in children with
moderate to severe dehydration. This result should be
interpreted with caution. In theory, children with more
severe dehydration are actually dehydrated longer, and they
may have had time to mobilize more intracellular fluid to
the plasma. More research is needed to find evidence for
this hypothesis.
In accordance with the recent guideline commissioned
by the National Institute for Health and Clinical Excellence
[8], laboratory tests should not be routinely used. Laboratory tests should only be performed in case of intravenous

Eur J Pediatr (2010) 169:883886

rehydration therapy, clinical evidence for hypernatremia,


and/or circulatory shock.
On the basis of our investigations, we conclude that
there is insufficient evidence to justify the use of plasma
water as a diagnostic tool in the assessment of dehydration
in children with acute gastroenteritis.

Conflict of interest None.

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