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Diagnosing Clinically Significant Dehydration in Children with Acute

Gastroenteritis Using Noninvasive Methods: A Meta-Analysis


Stephen B. Freedman, MDCM, MSc1, Ben Vandermeer, MSc2, Andrea Milne, MLIS2, and Lisa Hartling, PhD2, on behalf of the
Pediatric Emergency Research Canada Gastroenteritis Study Group*

Objective To determine the most accurate, noninvasive method of assessing dehydration.


Study design The following data sources were searched: electronic databases, gray literature, scientific meet-
ings, reference lists, and authors of unpublished studies. Eligible studies were comparative outpatient evaluations
that used an accepted reference standard and were conducted in developed countries in children aged <18 years
with gastroenteritis. Data extraction was completed independently by multiple reviewers before a consensus was
made.
Results Nine studies that included 1039 participants were identified. The 4-item Clinical Dehydration Scale (CDS),
the “Gorelick” score, and unstructured physician assessment were evaluated in 3, 2, and 5 studies, respectively.
Bedside ultrasound, capillary digital videography, and urinary measurements were each evaluated in one study.
The CDS had a positive likelihood ratio (LR) range of 1.87-11.79 and a negative LR range of 0.30-0.71 to predict
6% dehydration. When combined with the 4-item Gorelick Score, the positive LR was 1.93 (95% CI 1.07-3.49)
and negative LR was of 0.40 (95% CI 0.24-0.68). Unstructured dehydration assessment had a pooled positive
LR of 2.13 (95% CI 1.33-3.44) and negative LR of 0.48 (95% CI 0.28-0.82) to detect $5% dehydration.
Conclusions Overall, the clinical scales evaluated provide some improved diagnostic accuracy. However, test
characteristics indicate that their ability to identify children both with and without dehydration is suboptimal. Current
evidence does not support the routine use of ultrasound or urinalysis to determine dehydration severity. (J Pediatr
2015;-:---).

T
he cornerstone of gastroenteritis management is the assessment of dehydration, with therapy instituted based on
severity.1,2 However, dehydration is difficult to determine clinically,3 and change in body weight remains the “gold stan-
dard.”3 Unfortunately, recent well weights are rarely available,4 and the inaccuracy of available tests limits the ability of
clinicians to estimate the exact degree of dehydration.3 Consequently, research has focused on noninvasive methods of assessing
dehydration (eg, clinical scores,5-8 bedside ultrasound,4,9,10 urine ketones11). Scores, by using combinations of examination
findings, may perform better than individual signs at predicting dehydration.3 Popular examples include the “Gorelick”12
and Clinical Dehydration Scales (CDSs).5 These scales have been adopted, yet their ability to predict severe dehydration is sub-
optimal.13 For example, in a recent report, the 4- and 10-point Gorelick scale had sensitivities of only 64% and 21%, respec-
tively, for severe dehydration.13 Similarly, the ability of bedside ultrasound to assess intravascular volume status remains a topic
of debate.14 Conflicting opinions may relate to the study population and outcome measures used.
A systematic review and meta-analysis focused on research in developed countries can enhance the integration of evidence
into clinical care in such countries. A key focus of quality improvement efforts in children with gastroenteritis in developed
countries is to promote the use of oral rehydration therapy when appropriate in order to minimize the unnecessary adminis-
tration of intravenous fluids.15 Because diagnostic test characteristics (eg, predictive values) are dependent on the prevalence of
disease, evaluating tests of dehydration in the context of developed countries is important. With guidelines recommending that
therapy be tailored to clinical scores16,17 and bedside ultrasound becoming a
standard technology in pediatric emergency departments (EDs) across North
America,18 their roles must be defined.19,20 Thus, we conducted a systematic re- 1
From the Sections of Pediatric Emergency Medicine
and Gastroenterology, Alberta Children’s Hospital,
view of studies in which investigators evaluated the diagnostic test accuracy of Alberta Children’s Hospital Research Institute, University
2
noninvasive methods of dehydration assessment in developed countries. of Calgary, Calgary, Alberta, Canada; and Alberta
Research Centre for Health Evidence, Department of
Pediatrics, University of Alberta, Edmonton, Alberta,
Canada
*List of members of the Pediatric Emergency Research
Canada Gastroenteritis Study Group is available at www.
jpeds.com (Appendix).
Supported by the Canadian Institutes of Health Research
(Knowledge Synthesis grant 262955). L.H. holds a New
Ao Aorta Investigator Salary Award from the Canadian Institutes of
CDS Clinical Dehydration Scale Health Research. The authors declare no conflicts of in-
terest.
ED Emergency department
IVC Inferior vena cava 0022-3476/$ - see front matter. Copyright ª 2015 Elsevier Inc.
LR Likelihood ratio All rights reserved.
http://dx.doi.org/10.1016/j.jpeds.2014.12.029

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comes (eg diagnostic accuracy), source of funding, and re-


Methods
sults. Extracted data were entered into Microsoft Excel
(Microsoft, Redmond, Washington) worksheets. Disagree-
We followed a standard protocol for the conduct and report-
ments were resolved by consensus, or involving a third
ing of systematic reviews and meta-analyses, which was in
reviewer as required. The Quality Assessment of Diagnostic
keeping with the Preferred Reporting Items for Systematic re-
Accuracy Studies 2 tool27 was used to assess the methodo-
views and Meta-Analyses guidelines.21,22 An experienced
logic quality of the relevant studies. The Quality Assessment
medical librarian developed a search strategy in collaboration
of Diagnostic Accuracy Studies 2 includes 4 domains: patient
with the research team to identify studies examining the diag-
selection, index test, reference standard, and flow of patients
nostic accuracy of noninvasive methods of assessing dehydra-
through the study and the timing of the index tests and refer-
tion. We (1) systematically searched MEDLINE (1946 to
ence standard (flow and timing).28 Assessments regarding
April 2013), EMBASE (1980 to April 2013), the Cochrane
bias and applicability are made for each domain. Bias is as-
Central Register of Controlled Trials (April 2013) via the
sessed as low, unclear, or high risk; applicability is assessed
OvidSP platform, PubMed via the National Library of Med-
as low, unclear, or high concerns. Quality assessment was
icine (last 180 days), and for gray literature; (2) hand-
completed independently by 2 reviewers. Disagreements
searched appropriate journals and major, relevant scientific
were resolved by consensus, or involving a third reviewer as
meetings (Society for Pediatric Research 2010-2012, Amer-
required.
ican Academy of Pediatrics 2010-2012, Canadian Pediatric
We developed evidence tables to describe the studies
Society 2010-2012, and International Conference on Emer-
including information on design features, methodologic
gency Medicine 2012); (3) checked reference lists of relevant
quality, study populations, sample size, settings, dehydration
studies; and (4) contacted primary authors of published and
scores, and comparisons. For each of the included studies we
unpublished studies. The MEDLINE search strategy is ap-
extracted the raw data regarding true and false positives and
pended (Table I; available at www.jpeds.com). The search
negatives and constructed 2  2 tables to calculate sensitivity,
was not restricted by language or publication status. We
specificity, and likelihood ratios (LRs). Sensitivity and spec-
ran an updated search of the electronic databases in
ificity are measures of test accuracy. LRs are used to estimate
October 2014 to identify studies published after the first
the increased or decreased probability of disease (ie, dehydra-
search; no eligible studies were identified. All studies
tion) for a patient and can be used to refine clinical judgment.
contained in previous relevant systematic reviews were
The larger the positive LR, the greater the accuracy of the test
screened for inclusion.
and the greater the likelihood of disease after a positive test
Search result titles and abstracts were screened indepen-
result. In contrast, the smaller the negative LR, the lower
dently by 2 reviewers to identify potentially relevant citations.
the likelihood of disease after a negative test result.29 Sensitiv-
They were excluded when the title/abstract did not identify
ities, specificities, LRs, and predictive values are presented in
that the article addressed the accuracy of a noninvasive
a summary table that includes all dehydration assessment
method of assessing dehydration. The full text of all poten-
methods. We planned to analyze data using hierarchical sum-
tially relevant citations was obtained and assessed for inclu-
mary receiver-operating curves; however, an insufficient
sion by 2 independent reviewers using standard, predefined
number of studies examining any given test were identified
eligibility criteria. Disagreements were resolved by consensus.
to enable the use of this approach.30 Consequently, we
Decisions regarding inclusion and reasons for exclusion were
plotted the sensitivity and specificity of the individual studies
documented. Original studies were included if they: (1) eval-
in a receiver-operating curve space to graphically display the
uated children <18 years of age suspected to have dehydra-
relative accuracy of the different measures. We pooled LRs
tion; (2) examined the diagnostic accuracy of a noninvasive
using Maentel-Hansel methods and random effects models.
method of dehydration assessment against percent change
We were unable to formally assess for publication bias
in body weight between acute presentation and stable, rehy-
because of the small numbers of studies examining any given
drated, well weight (Table II)12; (3) were conducted in a
test.
developed country as defined by the United Nations in
2011—Australia, Canada, Europe, Japan, New Zealand, and
the US23; and (4) were conducted in an ED or similar Results
clinical setting. We included studies in which authors
focused on children with acute gastroenteritis. Comparative The electronic database search identified 1454 citations;
studies meeting the aforementioned criteria were included. 66 were considered potentially relevant based on their title/
Review articles were excluded. abstract (Figure 1; available at www.jpeds.com). Of these,
As is commonly performed, 1 reviewer extracted data us- 4 met inclusion. Five additional studies meeting eligibility
ing a structured form. Verification was performed by a sec- criteria were identified by reviewing the references of
ond reviewer for accuracy and completeness.24-26 The relevant studies (Table II). The median year of publication
following items were extracted: study characteristics (eg, was 2007. The 9 eligible studies included 1293 participants,
date of publication, clinical setting, country), participants of whom 1039 (80%) had both the diagnostic evaluation
(eg, age, sex), dehydration scores and comparisons, out- and the reference gold standard performed. Eight studies

2 Freedman et al
A Meta-Analysis
Diagnosing Clinically Significant Dehydration in Children with Acute Gastroenteritis Using Noninvasive Methods:

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Table II. Characteristics of studies included in systematic review
Author,
reference, Study design Number enrolled Setting Age, y, mean (SD) Dehydration
year, country (enrollment) (complete data) (patient type) or median [IQR] severity, % (n) Inclusion criteria Index test(s) evaluated Dehydration reference standard
Chen et al,4 prospective 112 (71) Hospital ED 5.3 (4.3)  <5% (43)  6 months to 18 years  Ultrasound (IVC:Ao)  Repeat weight once asymptomatic
2010, US cohort (NR) (outpatient)  $5% (28)  Acute gastroenteritis  Physician assessment for 48 h, 7-10 d postindex visit
(diarrhea with or without  Difference between ill weight and
vomiting, onset within well weight was used to calculate
7 days) % fluid loss at index visit
Gravel et al,7 prospective cohort 264 (219) Hospital ED 1.3 [0.75-2.3]  <3% (150)  1 mo to 5 y  CDS  Repeat weight once asymptomatic
2010, Canada (convenience) (outpatient)  3%-6% (40)  Vomiting or diarrhea for 48 h, 5-7 d postindex visit
 >6% (29) for <7 d  Difference between ill weight and
 Not requiring immediate well weight was used to calculate
physician assessment % fluid loss at index visit
(ie, severe dehydration
excluded)
Gorelick et al,12 prospective 225 (186) Hospital ED 1.1 [NR]  <5% (123)  1 month to 5 years  Gorelick scale  Stable weight reached when
1997, US cohort (outpatient)  5%-10% (52)  Vomiting, diarrhea, or 2 consecutive weights differed
(convenience)  $10% (11) poor fluid intake by <2%
 Mean of final 2 weights was
the “well” weight
 Subjects weighed at end of ED visit,
and again 48-72 h later, after
symptoms had resolved
 Daily visits occurred until stable
weight achieved
 Difference between ill weight and
well weight was used to calculate
% fluid loss at index visit
Jauregui et al,35 prospective cohort 148 (113) Hospital ED 6 [range: 1  <5% (101)  #18 y  CDS  Child was weighed before
2014, US (non-consecutive) (outpatient) mo-18 y]  $5% (12)  Acute diarrhea or  Gorelick scale intravenous fluid administration
vomiting, or suspicion  World Health and again at completion of ED visit
of dehydration Organization scale  “Well” weight was recorded upon
 Administered  Physician assessment discharge from ED or in hospitalized
intravenous rehydration children was recorded prior to
discharge from inpatient unit
 Difference between ill weight and
well weight was used to calculate
% fluid loss at index visit
Mackenzie et al,32 prospective 102 (102) Hospital Ward NR  <5% (76)  0-4 y  Physician assessment  Degree of dehydration
1989, Australia cohort (NR) (inpatient)  5%-10% (26)  Gastroenteritis was calculated by subtracting
 Previously well prerehydration weight from the
 Clinically assessed postrehydration weight
to be 5%-10% dehydrated  Children were reweighed daily

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until discharge
(continued )
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Table II. Continued
Author,
reference, Study design Number enrolled Setting Age, y, mean (SD) Dehydration
year, country (enrollment) (complete data) (patient type) or median [IQR] severity, % (n) Inclusion criteria Index test(s) evaluated Dehydration reference standard
Parkin et al,31 prospective cohort 141 (93) Hospital ED 1.5 [range:  <3% (49)  1-36 mo  CDS  Children were weighed
2010, Canada (convenience) (outpatient) 0.2-2.9]  $3-<6% (34)  Acute gastroenteritis before initiation of rehydration
 $6% (10) therapy and again when ED or
inpatient physician (if child
admitted to hospital) determined
that rehydration was complete
 Difference between ill weight and
well weight was used to calculate
% fluid loss at index visit
Shavit et al,34 prospective cohort 87 (83) Hospital ED 1.5 [0.9-2.8]  <5% (70)  1 mo-5 y  Digitally measured  Stable weight reached when
2006, Canada (convenience) (outpatient)  $5%-10% (12)  Acute gastroenteritis: capillary-refill time 2 consecutive weights differed
 $10% (1) diarrhea (with or without  Physician assessment by <2%


vomiting) #5 d  Mean of final 2 weights was

www.jpeds.com
 Some dehydration the “well” weight
 Subjects weighed at end of ED visit
and again 48-72 hours later, after
symptoms had resolved
 Daily visits occurred until stable
weight achieved
 Difference between ill weight and
well weight was used to calculate
% fluid loss at index visit
Steiner et al,11 prospective cohort 79 (75) Hospital ED 1.4 (NR)  <3% (25)  3-36 mo  Urine-specific gravity  Degree of dehydration was
2007, US (convenience) (outpatient)  3%-5% (34)  Acute gastroenteritis  Urine ketones calculated by subtracting
 $5% (16)  Suspected moderate prerehydration weight from the
dehydration postrehydration weight
 Administered  Difference between ill weight and
intravenous rehydration well weight was used to calculate
% fluid loss at index visit
Vega et al,33 prospective cohort 135 (97) Hospital ED 3.2 (range:  #5% (50)  All children (age not  Physician assessment  Subjects weighed within 72 hours
1997, US (consecutive) (outpatient) 2 wk-15 y)  6%-10% (30) specified) of index visit
 >10% (17)  Administered  If acute illness had resolved that
intravenous rehydration weight was deemed the “well”
 Gastroenteritis (85%); weight
stomatitis (4%);  If still ill, ongoing follow-up was
other (11%) scheduled
 Difference between ill weight and
well weight was used to calculate
% fluid loss at index visit

NR, not reported.


Sample size numbers reflect the total number of participants completing follow-up enabling a gold standard assessment of dehydration.

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Freedman et al
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recruited patients presenting for ED care. Six studies Physician clinical assessment of dehydration has been eval-
classified dehydration employing a <5%; 5%-10%, and uated by the use of several approaches. These include an
>10% scale; 3 used <3%; 3%-6%, and >6% as their overall hydration assessment by: (1) junior doctors, who
reference standard to reflect mild/moderate/severe were instructed to classify children as being 5%-10% dehy-
dehydration. Studies displayed significant heterogeneity in drated based on their hospital’s guideline32; (2) the fellow
terms of participant age, both at the younger and older or attending physician, by using a 9-item “standard clinical
extremes. scale”33; (3) the attending physician, blinded to ultrasound
findings and using an ordinal scale (<5%, 5%-10%,
Quality of Studies >10%)4; (4) the pediatric emergency physician, who esti-
Patient selection was rated as low risk of bias in 1 study; the mated the child’s degree of dehydration by using a 7-point
remaining studies were unclear or at high risk of bias Likert scale (very mild to very severe)34; and (5) having the
(Table III and Figure 2; available at www.jpeds.com). Six treating pediatric emergency medicine attending physicians
studies had unclear or high concerns about applicability record their clinical impression (1-10 scale) for percent dehy-
largely because information on patient selection was not dration.35
reported. The index test domain was at low risk of bias Excluding a study with 100% sensitivity because it
in 5 studies. One study had high risk of bias because included only children deemed to be 5%-10% dehydrated
researchers did not use prespecified thresholds for (ie, excluded children who might have been false negatives),32
classifying dehydration severity. Three studies were the sensitivity of this approach to detect $5% dehydration
assessed as unclear because they did not provide sufficient ranged from 33% to 78%. The pooled results from 4 studies
information to determine whether the researchers for positive and negative LRs were 2.13 (95% CI 1.33-3.44)
prespecified thresholds or whether the reference standard and 0.48 (95% CI 0.28-0.82), respectively. Overall accuracy
results were known when the index test was interpreted. ranged between 25% and 81% (Table IV).
All studies had low concerns regarding applicability. The Chen et al4 evaluated the accuracy of an inferior vena cava
domain of the reference standard was at low risk of bias (IVC) to aorta (Ao) ratio of <0.8 to predict $5% weight loss.
for 5 studies; 4 were rated as unclear because it was Although ultrasound had a negative LR value of 0.27, the
unknown whether the reference standard results were positive LR of 1.95 was significantly lower than both the
interpreted without knowledge of the index test result or CDS and the Gorelick scales for identifying >6% dehydra-
it was unclear when the well-weights were assessed. All tion. A single study also evaluated the ability of digital
studies had low concerns regarding applicability for this capillary refill to predict $5% body weight change. The au-
domain. Flow and timing was at low risk of bias for 4 thors reported an positive LR of 11.67 and negative LR of
studies; 5 were high risk of bias because a significant 0.00 and the greatest overall accuracy of any measure evalu-
proportion of participants were lost to follow-up or had ated (93%).34 The sensitivities and specificities of all assess-
incomplete measurements. ment methods identified are depicted in an ROC plot
(Figure 3).
Noninvasive Assessments
The CDS was evaluated in 3 studies. This 4-item scale was Interobserver Assessments (ie, Reproducibility)
derived in a cohort of 137 children 5(Tables IV and V; These were performed in 4 of the 9 studies and varied in size
Table V; available at www.jpeds.com). The authors used related to the entire cohort. Kappa values were lowest for the
formal approaches to derive the scale. Although diagnostic clinical measures—0.65 for the CDS and 0.69 for the Gorelick
accuracy was not reported in the derivation sample, scale.7,12 The values were greater for ultrasound (Pearson
subsequent work has conducted such analyses assigning correlation coefficient = 0.76)4 and digital capillary refill (in-
scores of 0, 1, or 2 for each item that is ranked along a traclass correlation = 0.99).34
continuum from normal to significantly abnormal.7,31
These studies (Table IV) revealed that a score of 0 had a Discussion
positive LR of 1.64-2.19 and negative LR of 0.79-0.84 to
predict <3% dehydration. The ability of the score to The practice of clinical medicine is founded on the reliability
predict $5% (or >6%) dehydration had positive LRs of history and physical examination to guide management.
ranging between 1.87 and 11.79 and negative LR ranged However, the evidence regarding the diagnostic accuracy of
between 0.30 and 0.71 (Figure 3). clinical examination is often lacking; pediatric dehydration is
The “Gorelick” scale, which formalized the dehydration no exception. The use of the CDS or the Gorelick scale both
evaluation via clinical features, uses 4- and 10-item scales.12 consistently reported accuracy values of >80% in identifying
Because of the overlap in clinical features between the CDS significant dehydration, although lower values were noted by
and the 4-item Gorelick score, these scores were combined Jauregui et al.35 Overall, the clinical scales evaluated provide
to generate pooled estimates with positive LR = 1.93 (95% some improved diagnostic accuracy. However, test character-
CI 1.07-3.49) and negative LR = 0.40 (95% CI 0.24-0.68). istics indicate that a substantial gap remains in how well the
The overall accuracy of these scales ranged between 57% scores predict the outcome of interest. Similarly, bedside ultra-
and 88% (Table IV). sound, which may aid in ruling out dehydration (LR negative
Diagnosing Clinically Significant Dehydration in Children with Acute Gastroenteritis Using Noninvasive Methods: 5
A Meta-Analysis
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Table IV. Results of studies included in systematic review (reference standard is weight change)
Predictive values LRs
Author, year, country N Index test Sensitivity, % (95% CI) Specificity, % (95% CI) Positive Negative Positive Negative Accuracy
CDS (4 items, 8 points)
Parkin et al,31 2010, Canada 93 CDS score = 0 0.32 (0.21-0.46) 0.85 (0.69-0.95) 79.17 42.03 2.19 0.79 51.61
<3% dehydration
93 CDS score = 1-4 0.67 (0.45-0.84) 0.42 (0.30-0.55) 28.57 78.38 1.15 0.79 48.39
3%-6% dehydration
93 CDS score = 5-8 0.50 (0.19-0.81) 0.90 (0.82-0.96) 38.46 93.75 5.19 0.55 86.02
>6% dehydration
Gravel et al,7 2010, Canada 219 CDS score = 0 0.33 (0.26-0.41) 0.80 (0.68-0.88) 78.13 35.48 1.64 0.84 47.95
<3% dehydration
219 CDS score = 1-4 0.75 (0.59-0.87) 0.38 (0.31-0.46) 21.28 87.18 1.21 0.66 44.75
3–6% dehydration
219 CDS score = 5-8 0.31 (0.15-0.51) 0.97 (0.94-0.99) 64.29 90.24 11.79 0.71 88.58


>6% dehydration
35
CDS score $2

www.jpeds.com
Jauregui et al, 2014, US 113 0.83 (0.52-0.98) 0.55 (0.45-0.65) 18.18 96.55 1.87 0.30 58.41
$5% dehydration
Physician clinical assessment
Vega et al,33 1997, US 97 Mild 0.74 (0.60-0.85) 0.70 (0.55-0.83) 72.55 71.74 2.48 0.37 72.16
<5% dehydration
97 Moderate 0.33 (0.17-0.53) 0.84 (0.73-0.92) 47.62 73.68 2.03 0.80 68.04
6%–10% dehydration
97 Severe 0.71 (0.44-0.90) 0.84 (0.74-0.91) 48.00 93.06 4.34 0.35 81.44
$10% dehydration
Chen et al,4 2010, US 71 Significant 0.78 (0.61-0.90) 0.51 (0.34-0.69) 62.22 69.23 1.60 0.43 64.79
$5% dehydration
Jauregui et al,37 2014, US 113 $5% dehydration 0.42 (0.15-0.72) 0.65 (0.55-0.75) 12.50 90.41 1.20 0.89 62.83
Mackenzie et al,37 1989, Australia 102 Moderate 5%-10% dehydration 1.00 (0.87-1.00) 0.00 (0.00-0.05) 25.49 n/a 1.00 n/a 25.49
Shavit et al,34 2006, Canada 83 Overall clinical assessment on 7-point Likert scale 0.77 (0.46-0.95) 0.81 (0.70-0.90) 43.48 95.00 4.14 0.28 80.72
Gorelick score
Gorelick et al,12 1997, US 186 4-item model score $2 0.79 (0.67-0.89) 0.87 (0.80-0.93) 75.76 89.43 6.25 0.24 84.66
$5% dehydration
186 4-item model score $3 0.82 (0.48-0.98) 0.83 (0.77-0.88) 23.08 98.67 4.85 0.22 83.07
$ 10% dehydration
186 10-item model score $3 0.87 (0.77-0.94) 0.82 (0.74-0.88) 71.43 92.66 4.88 0.15 83.87
$5% dehydration
186 10-item model score $7 0.82 (0.48-0.98) 0.87 (0.81-0.91) 28.13 98.70 6.23 0.21 86.56
$10% dehydration
Jauregui et al,35 2014, US 113 10-item score $2 0.75 (0.43-0.95) 0.55 (0.45-0.65) 16.67 94.92 1.68 0.45 57.52
$5% dehydration
World Health Organization Scale
Jauregui et al,35 2014, US 113 4-item scale $2 items 0.25 (0.05-0.57) 0.84 (0.76-0.91) 15.79 90.43 1.58 0.89 77.88
$5% dehydration
Bedside ultrasound
Chen et al,4 2010, US 71 IVC:Ao <0.80 on bedside ultrasound 0.85 (0.68-0.95) 0.56 (0.40-0.72) 62.22 81.48 1.95 0.27 69.44
Digital capillary refill time

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Freedman et al

Shavit et al,34 2006, Canada 83 DCRT $0.4 s 1.00 (0.75-1.00) 0.91 (0.82-0.97) 68.42 100.00 11.67 0.00 92.77
Laboratory measures
Steiner et al,11 2007, US 75 Urine-specific gravity, 1.030 (3%) 0.64 (0.49-0.77) 0.40 (0.21-0.61) 68.09 35.71 1.07 0.90 56.00
Steiner et al,11 2007, US 75 Urine-gravity, 1.030 (5%) 0.38 (0.15-0.65) 0.31 (0.19-0.44) 12.77 64.29 0.54 2.05 32.00

DCRT, digital capillary refill time; n/a, (not applicable) due to 0 cell counts (ie, no false negatives or true negatives).
- 2015 ORIGINAL ARTICLES

Figure 3. Receiver-operating curve plot showing combined sensitivity and specificity of the different diagnostic tests. WHO,
World Health Organization.

of 0.27), should not be used to confirm the presence of dehy- mance is—overall test accuracy (true positive + true nega-
dration (LR positive of 1.95). The most promising interven- tive) vs sensitivity or negative LR. The decision reached is
tion we identified was the use of digital videography likely based on one’s perspective on the number to over-
capillary refill time; given the paucity of data, however, further diagnose (ie, unnecessary intravenous fluids) to identify
research is required to confirm the preliminary findings. one case of severe dehydration. Clinicians must consider
Our findings are congruent with a previous review that the limited importance of distinguishing small increments
included studies in which authors evaluated dehydration of dehydration. This issue is highlighted in guidelines pub-
assessment in developed and developing countries.3 This re- lished by the Centers for Disease Control, which group
view concluded that the quantity and quality of research on children into none/minimal (<3%-5%), mild to moderate
dehydration assessment is extremely limited, with most (3%-9%), and severe ($9%) dehydration and tie manage-
studies being of only moderate sample size and at significant ment to these categories.2
risk of patient selection bias. Many were conducted at pedi- Ultrasound has been touted as having the potential to serve
atric institutions and enrolled exclusively children deemed as a useful adjunct for this clinical dilemma.36 In the single
to be dehydrated and those needing rehydration. This high- study identified,4 a pair of investigators obtained transverse
lights how study populations may not reflect the real-world images of the IVC and the Ao and then calculated their ratio
situation, where clinicians must identify the small number (IVC/Ao). The authors reported that an IVC/Ao cut-off of 0.8
of children with significant dehydration from those who produced a sensitivity of 86%, a specificity of 56%, and a pos-
are not dehydrated. itive predictive value of 62% for the diagnosis of significant
When considering our findings, it is important to dehydration. These characteristics are not superior to clinical
consider what the most important measure of test perfor- dehydration scales, and less than two-thirds of test-positive
Diagnosing Clinically Significant Dehydration in Children with Acute Gastroenteritis Using Noninvasive Methods: 7
A Meta-Analysis
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patients will have significant dehydration. Thus, there is 5. Friedman JN, Goldman RD, Srivastava R, Parkin PC. Development of a
insufficient evidence to support the routine use of ultrasound clinical dehydration scale for use in children between 1 and 36 months of
age. J Pediatr 2004;145:201-7.
due to the potential to result in “overtreatment” if test char-
6. Bailey B, Gravel J, Goldman RD, Friedman JN, Parkin PC. External vali-
acteristics are not considered. More recent work has also dation of the clinical dehydration scale for children with acute gastroen-
concluded that the IVC and Ao measurements by bedside ul- teritis. Acad Emerg Med 2010;17:583-8.
trasound are not reliable indicators of intravascular volume as 7. Gravel J, Manzano S, Guimont C, Lacroix L, Gervaix A, Bailey B. Multi-
determined by central venous pressure.14 Digital capillary center validation of the clinical dehydration scale for children [in
French]. Arch Pediatr 2010;17:1645-51.
refill time has only been described in a single study.34
8. Goldman RD, Friedman JN, Parkin PC. Validation of the clinical dehy-
The present study has several potential limitations. The dration scale for children with acute gastroenteritis. Pediatrics 2008;122:
greatest challenge in quantifying dehydration severity is the 545-9.
gold standard. Although this study required, in keeping with 9. Levine AC, Shah SP, Umulisa I, Munyaneza RB, Dushimiyimana JM,
expert opinion and previous studies,3,5,12,32,33 that postillness Stegmann K, et al. Ultrasound assessment of severe dehydration in chil-
dren with diarrhea and vomiting. Acad Emerg Med 2010;17:1035-41.
weight be used as the gold standard, the included studies
10. Kosiak W, Swieton D, Piskunowicz M. Sonographic inferior vena cava/
differed significantly in the precise day used as the reference aorta diameter index, a new approach to the body fluid status assessment
measure of stable post-illness weight (Table II).4,12,33,37 An in children and young adults in emergency ultrasound—preliminary
additional concern relates to the timing within a given day study. Am J Emerg Med 2008;26:320-5.
of rehydration weights, which are influenced by stooling, 11. Steiner MJ, Nager AL, Wang VJ. Urine specific gravity and other urinary
indices: inaccurate tests for dehydration. Pediatr Emerg Care 2007;23:
voiding, and feeding, especially in infants.3 Nonetheless, this
298-303.
study followed the use of this gold standard as the criteria 12. Gorelick MH, Shaw KN, Murphy KO. Validity and reliability of clinical
for defining true percent dehydration. Although this study signs in the diagnosis of dehydration in children. Pediatrics 1997;99:E6.
followed accepted methodologic standards for the conduct 13. Pringle K, Shah SP, Umulisa I, Mark Munyaneza RB,
of systematic reviews of diagnostic test accuracy including a Dushimiyimana JM, Stegmann K, et al. Comparing the accuracy of the
three popular clinical dehydration scales in children with diarrhea. Int
comprehensive search of the literature, there remains the
J Emerg Med 2011;4:58.
possibility that some unpublished studies may not have been 14. Ng L, Khine H, Taragin BH, Avner JR, Ushay M, Nunez D. Does bedside
identified. Although formally evaluating publication bias sonographic measurement of the inferior vena cava diameter correlate
through the use of funnel plots and statistical tests would be with central venous pressure in the assessment of intravascular volume
ideal, due to insufficient numbers of studies included in this in children? Pediatr Emerg Care 2013;29:337-41.
15. Santosham M, Keenan EM, Tulloch J, Broun D, Glass R. Oral rehydra-
review, a formal analysis of publication bias was not possible.
tion therapy for diarrhea: an example of reverse transfer of technology.
Overall, the accuracy of clinical assessments of dehydra- Pediatrics 1997;100:E10.
tion is suboptimal. Current evidence does not support the 16. Cincinnatti Children’s Hospital Medical Center Acute Gastroenteritis
routine use of ultrasound or urinalysis to determine dehydra- Team 2011. Evidence-Based Care Guideline for Prevention and Manage-
tion severity. Technological innovations, such as digital ment of Acute Gastroenteritis (AGE) in children age 2 mo to 18 yrs,
http://www.cincinnatichildrens.org/WorkArea/linkit.aspx?LinkIdentifier=
capillary refill, require further evaluation. The success of
id&ItemID=93672&libID=93365. Accessed October 16, 2014.
such work could enable clinicians to improve the care pro- 17. van den Berg J, Berger MY. Guidelines on acute gastroenteritis in chil-
vided to children at risk for dehydration. n dren: a critical appraisal of their quality and applicability in primary
care. BMC Fam Pract 2011;12:134.
We thank the following for their contributions to this project: Melanie 18. Vieira RL, Bachur R. Bedside ultrasound in pediatric practice. Pediatrics
Muise and Dion Pasichnyk for their assistance with screening, study se- 2014;133:1-3.
lection, data extraction, and verification, and Donna Dryden, MD, for 19. Levy JA, Bachur RG. Bedside ultrasound in the pediatric emergency
assistance with quality assessment. department. Curr Opin Pediatr 2008;20:235-42.
20. Leeson K, Leeson B. Pediatric ultrasound: applications in the emergency
Submitted for publication Aug 29, 2014; last revision received Oct 31, 2014; department. Emerg Med Clin North Am 2013;31:809-29.
accepted Dec 12, 2014. 21. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of In-
terventions. Version 5.0.2 [updated September 2009]. The Cochrane
Collaboration, 2009, www.cochrane-handbook.org. Accessed December
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22. Moher D, Liberati A, Tetzlaff J, Altman DG. The Prisma Group.
1. Guarino A, Albano F, Ashkenazi S, Gendrel D, Hoekstra JH, Preferred reporting items for systematic reviews and meta-analyses:
Shamir R, et al. European Society for Paediatric Gastroenterology, the PRISMA statement. BMJ 2009;339:b2535.
Hepatology, and Nutrition/European Society for Paediatric Infectious 23. Composition of macro geographical (continental) regions, geographical
Diseases evidence-based guidelines for the management of acute sub-regions, and selected economic and other groupings (footnote c).
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MMWR Recomm Rep 2003;52:1-16. Vandermeer B, et al. Systematic review: nonoperative and operative
3. Steiner MJ, DeWalt DA, Byerley JS. Is this child dehydrated? JAMA 2004; treatments for rotator cuff tears. Ann Intern Med 2010;153:246-55.
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4. Chen L, Hsiao A, Langhan M, Riera A, Santucci KA. Use of bedside ul- Donovan L. Benefits and harms of treating gestational diabetes
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Acad Emerg Med 2010;17:1042-7. tive Services Task Force and the National Institutes of Health

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26. Hartling L, Fernandes RM, Bialy L, Milne A, Johnson D, Plint A, with acute gastroenteritis. Clin Pediatr (Phila) 2010;49:235-9.
et al. Steroids and bronchodilators for acute bronchiolitis in the first 32. Mackenzie A, Barnes G, Shann F. Clinical signs of dehydration in chil-
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27. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, laboratory parameters for predicting percentage of dehydration in chil-
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accuracy studies. Ann Intern Med 2011;155:529-36. 34. Shavit I, Brant R, Nijssen-Jordan C, Galbraith R, Johnson DW. A novel
28. Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The devel- imaging technique to measure capillary-refill time: improving diagnostic
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29. Jaeschke R, Guyatt GH, Sackett DL. Users’ guides to the medical litera- External validation and comparison of three pediatric clinical dehydra-
ture. III. How to use an article about a diagnostic test. B. What are the tion scales. PLoS One 2014;9:e95739.
results and will they help me in caring for my patients? The Evidence- 36. Chen L, Kim Y, Santucci KA. Use of ultrasound measurement of the infe-
Based Medicine Working Group. JAMA 1994;271:703-7. rior vena cava diameter as an objective tool in the assessment of children
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Zwinderman AH. Bivariate analysis of sensitivity and specificity pro- 37. Mackenzie A, Barnes G. Randomised controlled trial comparing oral and
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Diagnosing Clinically Significant Dehydration in Children with Acute Gastroenteritis Using Noninvasive Methods: 9
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Appendix

Additional members of the Pediatric Emergency Research


Canada Gastroenteritis Study Group include:
David Johnson, MD (Alberta Children’s Hospital, Univer-
sity of Calgary, Alberta Children’s Hospital Research Insti-
tute, Calgary, AB), Karen Black, MD (University of British
Columbia, Vancouver, BC), Robert Porter, MD (Janeway
Children’s Hospital and Rehabilitation Centre, Memorial
University, St. John’s NL), Gary Joubert, MD (Schulich
School of Medicine & Dentistry, Children’s Health Research
Institute, London Health Sciences Centre, Western Univer-
sity, London, ON), Serge Gouin, MDCM (Universite de
Montreal, Centre Hospitalier Universitaire Sainte-Justine,
Montreal, QC), Quynh Doan, MDCM, MHSc, PhD (Child
& Family Research Institute, BC Children’s Hospital, Univer-
sity of British Columbia, Vancouver, BC), Janie Williamson,
RN (Alberta Children’s Hospital, University of Calgary, Cal-
gary, AB), Lynell Aucoin, RN (Women and Children’s Health
Research Institute, University of Alberta, Edmonton, AB), El-
eanor Fitzpatrick, BScN, MN (IWK Health Centre, Dalhousie
University, Halifax, NS), Mona Jabbour, MD (Children’s
Hospital of Eastern Ontario, Children’s Hospital of Eastern
Ontario Research Institute, University of Ottawa, Ottawa,
ON), and Terry Klassen, MD (Manitoba Institute of Child
Health, Winnipeg Regional Health Authority, University of
Manitoba, Winnipeg, MB).

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Table I. Search strategy for Medline via Ovid


MeSH and keywords for gastroenteritis:
1. exp Gastroenteritis/
2. Rotavirus/
3. Rotavirus Infections/
4. exp Norovirus/
5. exp Diarrhea/
6. Vomiting/
7. gastroenterit*.tw.
8. (diarrhea or diarrhoea).tw.
9. vomit*.tw.
10. gastritis.tw.
11. or/1-10 [MeSH and keywords for Gastro—without dehydration] (267,727)
MeSH and keywords for body fluids, body weight, and dehydration:
12. exp Body Fluids/
13. exp Body Weight/
14. Dehydration/
15. ((change* or loss*) adj3 body weight).tw.
16. ((fluid* or water) adj3 (status or volume)).tw.
17. dehydrat*.tw.
18. or/12-17 [MeSH and keywords for body fluids/weight] (628,497)
MeSH and keywords for diagnostic methods:
19. Point-of-Care Systems/
20. Health status indicators/
21. “Severity of Illness Index”/
22. Diagnostic Techniques, Digestive System/
23. exp Ultrasonography/
24. ((“point of care” or bedside or emergenc*) adj3 (ultrasound or sonograph* or ultrasonograph* or US)).tw.
25. (severit* adj3 (scale* or score* or rating or rate* or test)).tw.
26. or/19-25 [MeSH or keywords r/t US or dehydration scores] (415,155)
27. and/11,18,26 [GE + body weight/fluid + assessment tools] (381)
28. limit 27 to “all child (0 to 18 years)” (199)
29. exp Child/
30. exp Infant/
31. Adolescent/
32. Minors/
33. exp pediatrics/
34. (infant* or child* or adolescen* or teen* or youth* or young or p?ediatric* or juvenile*).tw.
35. or/29-34 [MeSH and keywords for child age group] (3,112,375)
36. and/27,35 [application of child age limit] (209)
37. or/28,36 [combination of Medline + manual age limit filters] (209)
38. remove duplicates from 37 (206)

MeSH, Medical Subject Headings.

Diagnosing Clinically Significant Dehydration in Children with Acute Gastroenteritis Using Noninvasive Methods: 9.e2
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Table III. Methodologic quality of included studies using QUADAS-2
1. Patient selection* 2. Index test* 3. Reference standard* 4. Flow and timing*
b. index
c. risk d. concerns c. risk d. concerns a. likely results c. risk d. concerns c. all included d. concerns
Author, a. b. of of a. reference results of of to not of of in of
year sample exclusion bias applicability not known b. threshold bias applicability classify known bias applicability a. interval b. same standard analysis applicability
Chen No Yes High Low Yes Yes Low Low Yes Yes Low Low Yes Yes No High
et al,4 2010
Gravel No U U U Yes Yes Low Low Yes Yes Low Low Yes Yes No High
et al,7
2010
Gorelick No Yes High High Yes U U Low Yes U U Low Yes Yes No High
et al,12
1997
Jauregui No No High High Yes No High Low U Yes U Low Yes Yes No High


et al,35

www.jpeds.com
2014
Mackenzie et al,37 U U U High Yes Yes Low Low Yes Yes Low Low Yes Yes Yes Low
1989
Parkin No U High Low U Yes U Low U U U Low Yes Yes Yes Low
et al,31
2010
Shavit et al,34 2006 No Yes High Low Yes Yes Low Low Yes Yes Low Low Yes Yes Yes Low
Steiner No Yes High High U U U Low U U U Low Yes Yes Yes Low
et al,11
2007
Vega et al,33 1997 Yes Yes Low High Yes Yes Low Low Yes Yes Low Low Yes Yes No High

QUADAS-2, Quality Assessment of Diagnostic Accuracy Studies 2; U, unclear.


*QUADAS-2 domain descriptions: 1.a. Random or consecutive sample; 1.b. Did the study avoid inappropriate exclusions?; 1.c. Was the study a low risk of bias?; 1.d.Is the study applicable?; 2.a. Reference standard results not known; 2.b. Prespecified threshold; 2.c.
Was the study a low risk of bias?; 2.d. Is the study applicable?; 3.a. Likely to classify target patients; 3.b. Index test results not known; 3.c. Was the study a low risk of bias?; 3.d. Is the study applicable?; 4.a. Interval between tests; 4.b. Same standard for all patients;
4.c. All patients included in analysis; 4.d. Was the study a low risk of bias?.

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Table V. Description of measurement scales, scores, and technological devices used to assess dehydration
Study where scale/
Scale or score score is used Description Items
CDS Gravel 2010 4 items General appearance (0/1/2 points)
Jauregui 2014 Score range 0-8 points Eyes (0/1/2 points)
Parkin 2010 Grouped as 0 = no dehydration; 1-4 = some Mucous membranes (0/1/2 points)
dehydration; 5-8 moderate–to-severe dehydration Tears (0/1/2 points)

Physician’s clinical Chen 2010 Vega/Chen Vega/Chen


assessment Jauregui 2014 Mild: #5% General appearance
Mackenzie 1989 Moderate: 6%-9% Radial pulse
Shavit 2006 Severe: $10% Respirations
Vega 1997 Mackenzie Anterior fontanel
5%-7%: any clinical signs Blood pressure
7%-10%: obvious signs Skin turgor
>10%: circulatory failure Eyes
Shavit Tears
Overall clinical assessment that uses 7-point Likert scale Mucous membranes
Mackenzie
General appearance
Peripheral perfusion
Respirations
Anterior fontanelle
Urine output
Skin turgor
Eyes
Tears
Mucous membranes
Thirst
Shavit
Overall clinical assessment that
uses 7-point Likert scale

“Gorelick” score Gorelick 1997 4-Item Model General appearance


Jauregui 2014 Score range 0-4 points Radial pulse
$5% dehydration: 2 or more points Respirations
$10% dehydration: 3 or more points Skin turgor
10-Item Model Eyes
Score range 0-10 points Tears
$5% dehydration: 3 or more points Mucous membranes
$10% dehydration: 7 or more points Capillary refill
Heart rate
Urine output

Bedside ultrasound Chen 2010 IVC and Ao diameters measured using C60 IVC:Ao using cut-off of 0.80 to
curvilinear probe over subxiphoid region indicate significant dehydration
Transverse image of vessels obtained
Maximal IVC diameter (expiratory phase)
Maximal Ao diameter (systole)

Digital capillary refill Shavit 2006 Hand raised slightly above level of heart DCRT $0.4 s
time (DCRT) Filmed fingertip using digital video camera, with
customized graphic software
“Frame-by-frame” analysis of exact color
Lightly pressed small rod against fingertip for 5 s and then released it
Compares subsequent frame with “precompression” frame until an
exact match is achieved (“recovery frame”)
Software calculates time between release and recovery frame = DCRT

Urine testing Steiner 2007 Visual calorimetric analysis at the bedside (performed by nurse or Urine ketones
physician) with Multistix – 10 SG urinalysis strips Urine specific gravity

IVC, Inferior Vena Cava; Ao, Aorta; DCRT, Digital Capillary Refill Time.

Diagnosing Clinically Significant Dehydration in Children with Acute Gastroenteritis Using Noninvasive Methods: 9.e4
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Figure 1. Flow diagram of study selection process. PICO, population intervention comparison outcome. From: Moher D, Liberati
A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA
statement. PLoS Med 2009; 6: e1000097. For more information, visit www.prisma-statement.org.

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Figure 2. QUADAS-2 risk of bias and applicability assessment, by domain. A, QUADAS-2 assessment of risk of bias by domain.
B, QUADAS-2 assessment of applicability by domain. QUADAS-2, Quality Assessment of Diagnostic Accuracy Studies 2.

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