ORIGINAL PAPER

Plasma water as a diagnostic tool in the assessmentof 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 essentialfor management of acute gastroenteritis. Plasma waterwas assessed as a diagnostic tool in children with acutegastroenteritis and dehydration admitted to hospital. In aprospective cohort study, 101 patients presenting at theemergency department with dehydration were included.Clinical assessment, routine laboratory tests, and plasmawater measurement were performed. Plasma water wasmeasured as a percentage of water content using dryweight method. During admission, patients were rehy-drated in 12 h. Weight gain at the end of the rehydrationperiod and 2 weeks thereafter was used to determine thepercentage of weight loss as a gold standard for theseverity of dehydration. Clinical assessment of dehydra-tion was not significantly associated with the percentageof 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 thepercentage of weight loss. Plasma water did not correlatewith the percentage of weight loss. On the basis of thepresented data, plasma water should not be used as a

diagnostic tool in the assessment of dehydration inchildren with acute gastroenteritis.

Keywords Plasma water . Dehydration . Diagnosis .

Gastroenteritis . Children

Introduction

Dehydration is the most important complication of acutegastroenteritis, and it is the major reason for hospitaladmission [6, 14].

The golden standard for the assessment of the severity ofdehydration is the percentage loss in body weight [1, 5, 6,10, 14, 15], as measured by the difference between weighton admission and at 2 weeks after discharge, divided byweight at 2 weeks after discharge. Several clinical scoreshave been developed [5, 10]. According to the clinicalscore of the American Academy of Pediatrics (AAP) [1],patients are classified into three subgroups: mild dehydra-tion (3–5%), moderate dehydration (6–9%), and severedehydration (>10%) [1, 6]. Clinical scores for dehydrationtend to underestimate the severity of dehydration and showonly moderate agreement between observers [6, 15].

It is recommended to perform laboratory tests indehydrated children if intravenous rehydration therapy isstarted, if there are signs and symptoms of increased serumsodium and in circulatory shock [6, 12]. Variables that arecorrelated best with the percentage of weight loss are:bicarbonate, blood urea nitrogen, and low pH in combina-tion with a high base excess [3, 6, 9, 10, 14, 15]. However,none of the laboratory tests studied and presented inliterature today can accurately estimate the percentage ofweight loss in a general pediatric practice [12].

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 Netherlandse-mail: groenewegm@maasstadziekenhuis.nl

R. W. Wulkan :R. Verwers :M. NeeleDepartment of Clinical Chemistry, Maasstad Hospital,Rotterdam, The Netherlands

W. C. J. HopDepartment of Biostatistics, Erasmus Medical Centre,Rotterdam, The Netherlands

Eur J Pediatr (2010) 169:883–886DOI 10.1007/s00431-010-1140-8

In dehydration, the percentage of weight loss wasdirectly associated with the percentage of plasma volumelost [4, 13]. It was, therefore, hypothesized that plasmawater may reflect the severity of dehydration. In 1952,Katcher et al. [4] studied plasma water in infants withdehydration. Plasma water was low in dehydrated childrenbut recovered soon after rehydration [7].

In this study, we evaluated plasma water as a diagnostictool in the assessment of dehydration in children with acutegastroenteritis admitted to hospital with moderate to severedehydration.

Methods

The study was approved by the Medical Ethics Committeeof the Maasstad Hospital Rotterdam. Between March 2006and June 2008, all patients with acute gastroenteritis anddehydration visiting the Emergency Department of theMaasstad Hospital Rotterdam were asked to participate inthe study. Exclusion criteria were: underlying metabolicdisorders (e.g., diabetes mellitus), diabetes insipidus, andrenal disease. Severity of dehydration was estimated on thebasis of clinical assessment according to the practiceparameter of the AAP [1], consisting of the followingvariables: blood pressure, quality of pulses, heart rate, skinturgor, depth of fontanel, humidity of mucous membranes,depth of eyes, capillary refill time, mental status, urineoutput, and thirst. Total scores consisted of sum of allvariables ranging from one to three per variable. Plasmawater was determined using a dry weight method (Sartori-us® Technologies B.V. Eindhoven, the Netherlands). Themeasurement takes 50 µL of heparin plasma and iscompleted in 3 min. The plasma was evaporated to dryness(constant weight) by infrared radiation. Before and duringevaporation, the sample weight was measured by automatedweighing. The percentage of initial water content was thencalculated from the wet and dry weight. From every bloodsample, the plasma water was calculated twice (duplomeasurements). The coefficient of variation calculated from50 measurements in duplicate is 0.5%. The followinglaboratory tests were performed: sodium, potassium, chlo-ride, blood urea nitrogen (BUN), creatinine, and venousblood gas analysis.

After clinical assessment of the severity of dehydration,all patients were rehydrated in 12 h. Patients were weighedbefore treatment, after 12-h rehydration and daily untildischarge and 2 weeks after discharge at the outpatientclinic of the Maasstad Hospital Rotterdam. The goldenstandard for dehydration was based on weight gain afterrehydration (difference between weight on admission and at2 weeks after discharge divided by weight at 2 weeks afterdischarge). Results of plasma water measurements in

dehydrated patients were compared to plasma watermeasurements of healthy controls (n=12), visiting theoutpatient clinic for functional disorders.

Statistical analysis

Two-tailed Wilcoxon rank-sum test was used to test clinicalvariables (mental status, quality of pulses, quality of breath-ing, skin turgor, fontanel, mucous membranes, eyes, extrem-ities, urine output, thirst, capillary refill time) with thepercentage of weight loss (data not shown). Associationsbetween continuous variables (all laboratory tests, including:plasma water, sodium, potassium, chloride, BUN, serumcreatinine, and venous blood gas analysis) are investigatedusing Spearman correlation coefficients. P=0.05 (two-sided)was considered the limit of significance.

Results

One hundred one patients (46 girls) were included in thestudy between March 2006 and June 2008. Demographicdata of all 101 patients are listed in Table 1. Fifty-eightof patients were younger than 2 years of age, 32 were 2–5 years old, and 11 patients were older than 5 years. For32 children, the percentage of weight loss could not bedetermined because of missing data. Demographic data ofthese 32 children did not differ from the total group (datanot shown). According to the percentage of weight loss,13/69 patients were slightly dehydrated (less than 3%), 18/69 were mildly dehydrated (3–5%), 12/69 moderately

Total (n=101) Parameter

Sex

Boy 55

Girl 46

Age

<2 years 58

2–5 years 32

5–12 years 11

Percentage of weight loss

<3% 13

3–5% 18

6–9% 12

9% 25

Not evaluable 33

Duration of admission

Median 3 days

Range 1–10 days

Table 1 Demographics andclinical characteristics

884 Eur J Pediatr (2010) 169:883–886

dehydrated (6–9%), and 26/69 severely dehydrated (morethan 9%).

The median duration of admission was 3 days (range 1–10 days; Table 1). Duplo measurements of plasma watershowed good reproducibility with an intraclass correlationof 0.95 (data not shown).

A decreased level of consciousnesses was significantlycorrelated with the percentage of weight loss (p<0.05, two-tailed Wilcoxon rank-sum test). All other clinical signs didnot significantly correlate with the percentage of weightloss (data not shown). Blood urea nitrogen (r=0.3, p=0.03,spearman correlation), base excess (r=−0.31, p=0.03), andserum bicarbonate (r=0.32, p=0.02; Fig. 1) significantlycorrelated with the severity of dehydration.

Plasma water did not significantly correlate with thepercentage of weight loss (r=0.21, p=0.98). In addition, nodifference in plasma water levels was found betweenpatients and healthy controls (Fig. 2).

Subgroup analysis showed that there was a trend towardsa higher percentage of plasma water in moderate to severedehydration (>6% weight loss).

Discussion

This is the first study in which plasma was measured in alarge group of children with acute gastroenteritis anddehydration.

This study shows that clinical assessment of dehydrationdoes not reflect the percentage of weight loss and that ureanitrogen, bicarbonate, and base excess are significantlycorrelated with the percentage of weight loss. Thesefindings are in accordance with studies by others [3, 6, 9,10, 12, 14, 15].

Percentage of weight loss

20,010,00,0-10,0

Bas

e E

xces

s (

mm

ol/l

)0

-5

-10

-15

-20 p<0.02

Percentage of weight loss

20,010,00,0-10,0

Blo

od

ure

a n

itro

gen

(m

mo

l/l)

25,0

20,0

15,0

10,0

5,0

0,0 p<0.02

Percentage of weight loss

20,010,00,0-10,0

Bic

arb

on

ate

(m

mo

l/l)

25

20

15

10

5 p<0.02

Fig. 1 Spearman correlation of percentage of weight loss with baseexcess (−0.31 ; p=0.03), blood urea nitrogen (0.3; p=0.03), and serumbicarbonate (0.32; p=0.02)

Percentage of weight loss

20,010,00,0-10,0

Pla

sma

wat

er (

%)

96

94

92

90

mean of controls +1 SD

mean of controls

mean of controls -1 SD

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

Eur J Pediatr (2010) 169:883–886 885

Plasma water was not correlated with the percentage ofweight loss. Subgroup analysis showed that there was atrend towards a higher percentage of plasma water inmoderate 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 gastroen-teritis and dehydration. The physiological regulation oftotal 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 experimen-tal animals and in healthy humans that it takes some timefor this complex regulatory system to find an equilibrium[2]. Hydration status can alter quickly in a response to rapidintake of a hypotonic fluid (e.g., water), and renal responseswill protect against fluid overload (by producing hypo-osmolar urine). In addition, the body will respond toalterations in plasma osmolality. If initial fluid loss alsoresults in electrolyte loss (like in acute gastroenteritis), theincrease in plasma osmolality will be only moderate, whichresults in an attenuated mobilization of intracellular fluid tothe plasma. Plasma water will increase more slowlyaccordingly. In addition, in a state of dehydration, rapidoral fluid intake can lead to rapid increase plasma water,before intracellular rehydration has started. We measuredplasma water at one moment in time in children with acutegastroenteritis and dehydration, and probably none of thesechildren’s fluid status was fully balanced. We, therefore,hypothesize that plasma water differs from child to childdependent of the actual fluid balance they are in themoment blood is drawn to measure plasma water. Factorslike oral fluid and electrolyte intake, the amount of ongoingfluid—and electrolyte losses and differences in body sizeand composition—may have greatly influenced our results[2, 11].

Subgroup analysis showed that there was a trend towardsa higher percentage of plasma water in children withmoderate to severe dehydration. This result should beinterpreted with caution. In theory, children with moresevere dehydration are actually dehydrated longer, and theymay have had time to mobilize more intracellular fluid tothe plasma. More research is needed to find evidence forthis hypothesis.

In accordance with the recent guideline commissionedby the National Institute for Health and Clinical Excellence[8], laboratory tests should not be routinely used. Labora-tory tests should only be performed in case of intravenous

rehydration therapy, clinical evidence for hypernatremia,and/or circulatory shock.

On the basis of our investigations, we conclude thatthere is insufficient evidence to justify the use of plasmawater as a diagnostic tool in the assessment of dehydrationin children with acute gastroenteritis.

Conflict of interest None.

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