Professional Documents
Culture Documents
JAMDA
journal homepage: www.jamda.com
Original Study
a b s t r a c t
Keywords: Objectives: Dehydration in older adults contributes to increased morbidity and mortality during hospi-
Dehydration talization. As such, early diagnosis of dehydration may improve patient outcome and reduce the burden
diagnosis on healthcare. This prospective study investigated the diagnostic accuracy of routinely used physical
older
signs, and noninvasive markers of hydration in urine and saliva.
hypovolemia
Design: Prospective diagnostic accuracy study.
osmolality
clinical Setting: Hospital acute medical care unit and emergency department.
Participants: One hundred thirty older adults [59 males, 71 females, mean (standard deviation) age ¼ 78
(9) years].
Measurements: Participants with any primary diagnosis underwent a hydration assessment within
30 minutes of admittance to hospital. Hydration assessment comprised 7 physical signs of dehydration
[tachycardia (>100 bpm), low systolic blood pressure (<100 mm Hg), dry mucous membrane, dry axilla,
poor skin turgor, sunken eyes, and long capillary refill time (>2 seconds)], urine color, urine specific
gravity, saliva flow rate, and saliva osmolality. Plasma osmolality and the blood urea nitrogen to creat-
inine ratio were assessed as reference standards of hydration with 21% of participants classified with
water-loss dehydration (plasma osmolality >295 mOsm/kg), 19% classified with water-and-solute-loss
dehydration (blood urea nitrogen to creatinine ratio >20), and 60% classified as euhydrated.
Results: All physical signs showed poor sensitivity (0%e44%) for detecting either form of dehydration,
with only low systolic blood pressure demonstrating potential utility for aiding the diagnosis of water-
and-solute-loss dehydration [diagnostic odds ratio (OR) ¼ 14.7]. Neither urine color, urine specific
gravity, nor saliva flow rate could discriminate hydration status (area under the receiver operating
characteristic curve ¼ 0.49e0.57, P > .05). In contrast, saliva osmolality demonstrated moderate diag-
nostic accuracy (area under the receiver operating characteristic curve ¼ 0.76, P < .001) to distinguish
both dehydration types (70% sensitivity, 68% specificity, OR ¼ 5.0 (95% confidence interval 1.7e15.1) for
water-loss dehydration, and 78% sensitivity, 72% specificity, OR ¼ 8.9 (95% confidence interval 2.5e30.7)
for water-and-solute-loss dehydration).
Conclusions: With the exception of low systolic blood pressure, which could aid in the specific diagnosis
of water-and-solute-loss dehydration, physical signs and urine markers show little utility to determine if
an elderly patient is dehydrated. Saliva osmolality demonstrated superior diagnostic accuracy compared
with physical signs and urine markers, and may have utility for the assessment of both water-loss and
water-and-solute-loss dehydration in older individuals. It is particularly noteworthy that saliva osmo-
lality was able to detect water-and-solute-loss dehydration, for which a measurement of plasma
osmolality would have no diagnostic utility.
Ó 2015 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
The study was funded by HydraDx Inc. The company was interested in iden- * Address correspondence to Neil P. Walsh, PhD or Matthew B. Fortes, College of
tifying if saliva indices other than those presented herein had utility for hydration Health and Behavioural Sciences, Bangor University, Bangor LL57 2PZ, UK.
assessment. MBF and PRB were employed as research assistants by HydraDx on this E-mail addresses: n.walsh@bangor.ac.uk (N.P. Walsh), m.fortes@bangor.ac.uk
study. (M.B. Fortes).
http://dx.doi.org/10.1016/j.jamda.2014.09.012
1525-8610/Ó 2015 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
222 M.B. Fortes et al. / JAMDA 16 (2015) 221e228
Fig. 1. Participant flow through the study. BUN, blood urea nitrogen.
variation for repeated sample plasma osmolality measurements assessing the length of time for the return of normal color). Each
was 0.7% (1.9 mOsm/kg). physical sign was assessed with the participant rested and seated
upright and assessed dichotomously.
Index tests
Clinical assessment of physical signs of dehydration. The clinical Saliva sample collection and analysis. Unstimulated whole saliva
assessment consisted of 7 physical signs of dehydration that are samples were collected using a pre-weighed Versi-sal collection
routinely used in Gwynedd Hospital; tachycardia (resting heart device (Oasis Diagnostics Corporation, Vancouver, WA) as previ-
rate >100 bpm), low resting systolic blood pressure (<100 mm ously described.29 Participants first swallowed in order to empty
Hg), dry mucous membrane (inside of the cheek, dry vs wet), the mouth of residual saliva, before saliva was collected by
axillary dryness (assessed by palpating the armpit, dry vs moist), placing the Versi-sal collection device under the tongue. Saliva
poor skin turgor (measured by pinching the skin on the dorsum of collection was performed with minimal orofacial movements and
the hand and observing if the tissue fold returned to normal accurately timed. After 4 minutes, the collection device was
immediately), presence of sunken eyes as assessed by the clinical inspected for volume of saliva by weighing it immediately (to the
research fellow, and long capillary refill time (>2 seconds, assessed nearest milligram) and subtracting the pre-weight. If the volume
by holding the patients hand at heart level and blanching the was insufficient for osmolality analysis (<25 mL), the swab was
participant’s right index finger using moderate pressure and replaced under the tongue for an additional 4 minutes. By
224 M.B. Fortes et al. / JAMDA 16 (2015) 221e228
assuming the density of saliva to be 1.00 g/mL, SFR was calcu- To assess the diagnostic accuracy of saliva and urine indices, and
lated by dividing the volume collected by the time of collection.24 clinical physical signs for assessment of hydration status, both water-
Saliva was recovered from the collection device by centrifugation loss, and water-and-solute-loss dehydration groups were separately
at 1500 g for 10 minutes and assessed immediately in duplicate compared with the euhydrated control group. Both dehydration
for saliva osmolality using a freezing point depression osmometer groups were also combined to form a generic dehydration group for
(Model 330 MO; Advanced Instruments). The analytical coeffi- comparison with euhydration. For all dichotomized clinical physical
cient of variation for repeated sample saliva osmolality mea- sign data, the following were calculated; area under the receiver
surements was 0.8% (0.9 mOsm/kg). operating characteristic curve (AUCROC) as a measure of global diag-
nostic accuracy, sensitivity, specificity, positive and negative likeli-
Urine sample collection and analysis. A mid-flow urine sample was hood ratios, and the diagnostic odds ratio (OR) generated by logistical
collected and immediately analyzed for urine color27 and urine regression. For continuous variable data (urine color, USG, SFR, and
specific gravity (USG) using a handheld refractometer (Atago saliva osmolality), the degree to which each variable could discrimi-
URC-Osmo refractometer, Atago Co, Ltd, Tokyo, Japan). nate between dehydration and euhydration was assessed using AU-
CROC. For variables that could distinguish hydration status, the single
Sample Size Calculation and Data Analysis cut-off value that provided the optimal discrimination was identified
as the point on the curve with the largest vertical displacement from
The desired sample size for dehydrated participants (n ¼ 20 the reference line, and sensitivity, specificity, overall diagnostic
water-loss only) was calculated using the following equation: accuracy, positive and negative likelihood ratios, and the diagnostic
OR were calculated. For all diagnostic analyses 95% CIs were con-
n ð1:96Þ2 pð1 pÞ structed. To compare AUCROC, a method was adopted that accounts
for the correlation between samples from the same individual.31
x2
Group data were analyzed using one-way analysis of variance. Data
Where p ¼ desired sensitivity (70%) as a proportion, and x ¼ desired were analyzed using Microsoft excel (Microsoft Corporation, Red-
confidence interval (CI) (20%) as a proportion.30 Assuming a prev- wood, WA), SigmaPlot version 12.0 (Systat Software, Inc, San Jose,
alence of impending water-loss dehydration (plasma osmolality CA), and SPSS version 20 (IBM Corporation, Armonk, NY) software.
295 mOsm/kg) of 17%,7 and allowing for an approximate one- Significance was accepted as P < .05 for all analysis of variance,
third exclusion rate from data analysis (because of missing refer- logistic regression, and AUCROC analyses.
ence tests, and comorbidities that preclude the use of the reference
standards), a total of 178 participants were recruited into the study.
Medical records for participants were accessed after enrollment Results
and because of potential influencing effects on the reference
standards assessed in this study, participants with a history of renal Participant Characteristics
disease (chronic kidney disease stage 1e5, n ¼ 24), or who were in
cardiac failure as diagnosed by a clinician (n ¼ 1) were excluded A total of 420 participants were screened for inclusion, with 242
from data analysis. Participants were also excluded from data excluded, largely because of ethical considerations of conducting the
analysis if the reference tests were not available (n ¼ 11), if they had research, or declining to take part (n ¼ 240, 57%), or because of
an abnormally low (<10) BUN:Cr, which may be indicative of renal swallowing problems (n ¼ 2, 1%). Therefore, 178 participants were
disease or the syndrome of inappropriate antidiuretic hormone enrolled into the study (n ¼ 85 males, n ¼ 93 females) with mean age
(n ¼ 8), or if they were taking glucocorticoid medication (n ¼ 4) (standard deviation) 78 (9) years. After further exclusions for data
which affects the validity of the BUN:Cr.10 Based on the reference analysis, data were analyzed for n ¼ 130 participants (n ¼ 59 males,
standards, participants with a presenting plasma osmolality 295 n ¼ 71 females; mean age 78 (9), range 60e101 years), of which
mOsm/kg were classified as having impending water-loss dehy- n ¼ 27 (21%) were classified as water-loss dehydrated, n ¼ 25 (19%)
dration.12,22 Of the remaining participants, those with a BUN:Cr were classified as water-and-solute-loss dehydrated, and n ¼ 78
20 in the absence of hypertonicity22 were classified as having (60%) were classified as euhydrated. Of the 27 participants in the
water-and-solute-loss dehydration, and the remaining participants water-loss only dehydration group, 10 also had an elevated BUN:Cr
formed the euhydrated control group (normal plasma osmolality (20). There were no differences between the groups for age
and BUN:Cr). (Table 1). By design, participants with water-loss dehydration had
Table 1
Group Data for Age, Blood Reference Tests, and Urine and Saliva Index Tests of Hydration
1.9 (0.7e5.0)
1.2 (0.5e3.0)
(0.7e4.2)
(0.7e4.3)
(0.7e6.7)
(0.2e2.7)
loss dehydration had elevated BUN:Cr compared with euhydrated
Diagnostic OR
control (Table 1).
1.7
1.7
2.2
0.8
Feasibility of Collecting Index Tests
0.8 (0.6e1.1)
0.9 (0.6e1.4)
(0.6e1.2)
(0.5e1.2)
(0.7e1.1)
(0.9e1.3)
Negative LR
All clinical physical sign assessments were conducted in all 130
participants. Saliva was collected in all but 4 participants (1 water-
Diagnostic Accuracy of Clinical Signs to Determine Both Forms of Dehydration in Combination, and Separately (Water-Loss Only, and Water-and-Solute Loss Dehydration) in Older Adults >60 Years
0.8
0.8
0.9
1.0
hydrated control). For these 4 participants SFR was recorded as zero,
and SFR data was therefore analyzed for n ¼ 130. There was adequate
1.6 (0.8e3.0)
1.1 (0.7e1.9)
(0.8e2.4)
(0.8e2.3)
(0.8e4.6)
(0.3e2.3)
saliva (>25 mL) to assess saliva osmolality in 98 participants (75%). In
Positive LR
comparison urine samples could not be collected in 45 participants,
who were unable to urinate within 30 minutes of the blood collec-
1.4
1.4
1.9
0.8
tion. One participant provided a urine sample containing blood,
confounding interpretation. Urine color and specific gravity were
0.56 (0.43e0.70)
0.52 (0.39e0.65)
(0.43e0.70)
(0.44e0.70)
(0.42e0.69)
(0.36e0.61)
therefore analyzed in 84 participants (65%).
Diagnostic OR AUCROC
Diagnostic Accuracy of Clinical Physical Signs
0.56
0.57
0.56
0.48
Diagnostic data for all 7 clinical physical signs for both types of
(0.5e3.1)
(0.5e3.2)
(0.1e2.7)
(0.5e3.5)
dehydration are shown in Table 2 and Figure 2. No clinical physical sign
in isolation could discriminate between euhydration and either form of
dehydration (AUCROC range 0.44e0.57). Individually, all clinical phys-
N/A
1.3
1.3
0.5
1.2
ical signs performed poorly in terms of detecting dehydration with
(0.7e1.3)
(0.6e1.3)
(0.9e1.2)
(0.8e1.2)
sensitivity ranging from 0%e44%. They did, however, generally perform
Negative LR
better at detecting euhydration, with specificity ranging from 60%e
1 (1)
99%. For detecting water-and-solute-loss dehydration, a low resting
0.9
0.9
1.1
1.0
systolic blood pressure (<100 mm Hg) demonstrated high diagnostic
odds and likelihood ratios [14.7 (95% CI 1.6e138.3) and 12.5 (95% CI
(0.6e2.1)
(0.7e2.0)
(0.1e2.5)
(0.5e2.7)
Water-Loss Only Dehydration
1.2
1.2
0.6
1.2
Diagnostic Accuracy of Urine and Saliva Indices
(0.40e0.65)
(0.40e0.66)
(0.35e0.60)
(0.39e0.64)
There were no differences between any of the 3 groups for urine
Diagnostic OR AUCROC
color, USG, or SFR (Table 1). Furthermore, when assessed using ROC
BP, blood pressure; HR, heart rate; LR, likelihood ratio; N/A, not assessed as sensitivity was 0%.
0.53
0.53
0.43
0.52
analyses, neither urine color, USG, nor SFR were able to discriminate
between dehydration and euhydration (AUCROC range 0.49e0.57, all
*P < .05 significantly associated with hydration status by logistic regression analysis.
P > .05, Table 3). Saliva osmolality was greater in participants with
1.0 (0.8e1.2) 1.0 (0.4e2.3)
(0.7e3.0)
(0.7e3.1)
(0.5e3.4)
(0.4e2.4)
both forms of dehydration than euhydrated control (P < .001, Table 1),
but more importantly, was able to distinguish both types of dehy-
1.4
1.5
1.2
1.0
dration separately from euhydration (AUCROC ¼ 0.76, P < .01 for both
types of dehydration individually and combined, Table 3). Based on
(0.7e1.2)
(0.6e1.1)
(0.8e1.1)
(0.8e1.2)
Negative LR
the ROC analysis, the saliva osmolality cut-off that provided the op-
timum balance between sensitivity and specificity was calculated as
95, 97, and 94 mOsm/kg for water-loss only, water-and-solute-loss
0.9
0.9
1.0
1.0
(0.8e2.0)
(0.8e2.0)
(0.5e2.8)
(0.5e2.0)
physical signs and urine indices for both types of dehydration in older
0.54
0.55
0.51
0.50
Discussion
(<100 mm Hg)
membrane
Sunken eyes
Dry mucous
Tachycardia
saliva osmolality was able to detect water-and-solute-loss dehydra- 20. Fletcher SJ, Slaymaker AE, Bodenham AR, Vucevic M. Urine colour as an index
of hydration in critically ill patients. Anaesthesia 1999;54:189e192.
tion, for which a measurement of plasma osmolality would have no 21. Shimizu M, Kinoshita K, Hattori K, et al. Physical signs of dehydration in the
diagnostic utility. The measurement of saliva osmolality has potential elderly. Intern Med 2012;51:1207e1210.
utility as a screening method to aid the diagnosis of impending 22. Stookey JD, Pieper CF, Cohen HJ. Is the prevalence of dehydration among
community-dwelling older adults really low? Informing current debate over
dehydration in older adults. the fluid recommendation for adults aged 70þyears. Public Health Nutr 2005;
8:1275e1285.
23. Hooper L, Bunn D, Jimoh FO, Fairweather-Tait SJ. Water-loss dehydration and
Acknowledgments aging. Mech Ageing Dev 2014;136-137:50e58.
24. Oliver SJ, Laing SJ, Wilson S, et al. Saliva indices track hypohydration during
The authors would like to thank Emma Tye for her assistance with 48h of fluid restriction or combined fluid and energy restriction. Arch Oral Biol
2008;53:975e980.
data collection, Dr. Frank Bellizzi, Dr. Andrew Goldstein, Dr. Ken 25. Walsh NP, Laing SJ, Oliver SJ, et al. Saliva parameters as potential indices of
Strahs, and Dr. John Donovan for their valuable input into the hydration status during acute dehydration. Med Sci Sports Exerc 2004;36:
research protocol, and to Betsi Cadwaladr University Health Board, for 1535e1542.
26. Walsh NP, Montague JC, Callow N, Rowlands AV. Saliva flow rate, total protein
facilitating this research. The authors would also like to thank all the
concentration and osmolality as potential markers of whole body hydration
patients who agreed to participate in this study. status during progressive acute dehydration in humans. Arch Oral Biol 2004;
49:149e154.
27. Armstrong LE, Maresh CM, Castellani JW, et al. Urinary indices of hydration
References status. Int J Sport Nutr 1994;4:265e279.
28. Cheuvront SN, Ely BR, Kenefick RW, Sawka MN. Biological variation and
1. Xiao H, Barber J, Campbell ES. Economic burden of dehydration among hos- diagnostic accuracy of dehydration assessment markers. Am J Clin Nutr 2010;
pitalized elderly patients. Am J Health Syst Pharm 2004;61:2534e2540. 92:565e573.
2. Warren JL, Bacon WE, Harris T, et al. The burden and outcomes associated with 29. Fortes MB, Diment BC, Di Felice U, Walsh NP. Dehydration decreases saliva
dehydration among US elderly, 1991. Am J Public Health 1994;84:1265e1269. antimicrobial proteins important for mucosal immunity. Appl Physiol Nutr
3. Bhalla A, Sankaralingam S, Dundas R, et al. Influence of raised plasma osmo- Metab 2012;37:850e859.
lality on clinical outcome after acute stroke. Stroke 2000;31:2043e2048. 30. Banoo S, Bell D, Bossuyt P, et al. Evaluation of diagnostic tests for infectious
4. O’Neill PA, Faragher EB, Davies I, et al. Reduced survival with increasing plasma diseases: General principles. Nat Rev Microbiol 2008;6:S16eS26.
osmolality in elderly continuing-care patients. Age Ageing 1990;19:68e71. 31. Hanley JA, McNeil BJ. A method of comparing the areas under receiver operating
5. Rowat A, Graham C, Dennis M. Dehydration in hospital-admitted stroke pa- characteristic curves derived from the same cases. Radiology 1983;148:839e843.
tients: Detection, frequency, and association. Stroke 2012;43:857e859. 32. Stookey JD, Purser JL, Pieper CF, Cohen HJ. Plasma hypertonicity: Another
6. Stookey JD. High prevalence of plasma hypertonicity among community- marker of frailty? J Am Geriatr Soc 2004;52:1313e1320.
dwelling older adults: Results from NHANES III. J Am Diet Assoc 2005;105: 33. Gorelick MH, Shaw KN, Murphy KO. Validity and reliability of clinical signs in
1231e1239. the diagnosis of dehydration in children. Pediatrics 1997;99:E6.
7. Thomas DR, Tariq SH, Makhdomm S, et al. Physician misdiagnosis of dehy- 34. Steiner MJ, DeWalt DA, Byerley JS. Is this child dehydrated? JAMA 2004;291:
dration in older adults. J Am Med Dir Assoc 2004;5:S30eS34. 2746e2754.
8. Armstrong LE. Assessing hydration status: The elusive gold standard. J Am Coll 35. Sarhill N, Walsh D, Nelson K, Davis M. Evaluation and treatment of cancer-
Nutr 2007;26:575Se584S. related fluid deficits: Volume depletion and dehydration. Support Care Can-
9. Mange K, Matsuura D, Cizman B, et al. Language guiding therapy: The case of cer 2001;9:408e419.
dehydration versus volume depletion. Ann Intern Med 1997;127:848e853. 36. Cheuvront SN, Kenefick RW. Dehydration: Physiology, assessment and per-
10. Thomas DR, Cote TR, Lawhorne L, et al. Understanding clinical dehydration and formance effects. Compr Physiol 2014;4:257e285.
its treatment. J Am Med Dir Assoc 2008;9:292e301. 37. Walsh NP, Fortes MB, Raymond-Barker P, et al. Is whole-body hydration an
11. McGee S, Abernethy WB III, Simel DL. The rational clinical examination. Is this important consideration in dry eye? Invest Ophthalmol Vis Sci 2012;53:
patient hypovolemic? JAMA 1999;281:1022e1029. 6622e6627.
12. Hooper L, Attreed NJ, Campbell WW, et al. Clinical and physical signs for 38. Steiner MJ, Nager AL, Wang VJ. Urine specific gravity and other urinary
identification of impending and current water-loss dehydration in older people indices: Inaccurate tests for dehydration. Pediatr Emerg Care 2007;23:
(Protocol). Cochrane Database Syst Rev 2012;(2):CD009647. 298e303.
13. Vivanti A, Harvey K, Ash S, Battistutta D. Clinical assessment of dehydration in 39. Obuchowski NA, Lieber ML, Wians FH Jr. ROC curves in clinical chemistry: Uses,
older people admitted to hospital: What are the strongest indicators? Arch misuses, and possible solutions. Clin Chem 2004;50:1118e1125.
Gerontol Geriatr 2008;47:340e355. 40. Woods DL, Mentes JC. Spit: Saliva in nursing research, uses and methodological
14. Vivanti A, Harvey K, Ash S. Developing a quick and practical screen to improve considerations in older adults. Biol Res Nurs 2011;13:320e327.
the identification of poor hydration in geriatric and rehabilitative care. Arch 41. Miller CS, Foley JD, Bailey AL, et al. Current developments in salivary di-
Gerontol Geriatr 2010;50:156e164. agnostics. Biomark Med 2010;4:171e189.
15. Chassagne P, Druesne L, Capet C, et al. Clinical presentation of hypernatremia in 42. Benelli U, Nardi M, Posarelli C, Albert TG. Tear osmolarity measurement using
elderly patients: A case control study. J Am Geriatr Soc 2006;54:1225e1230. the TearLab Osmolarity System in the assessment of dry eye treatment effec-
16. Wakefield B, Mentes J, Diggelmann L, Culp K. Monitoring hydration status in tiveness. Cont Lens Anterior Eye 2010;33:61e67.
elderly veterans. West J Nurs Res 2002;24:132e142. 43. Fortes MB, Diment BC, Di Felice U, et al. Tear fluid osmolarity as a
17. Weinberg AD, Minaker KL. Dehydration. Evaluation and management in older potential marker of hydration status. Med Sci Sports Exerc 2011;43:
adults. Council on Scientific Affairs, American Medical Association. JAMA 1995; 1590e1597.
274:1552e1556. 44. Ely BR, Cheuvront SN, Kenefick RW, Sawka MN. Limitations of salivary osmo-
18. Eaton D, Bannister P, Mulley GP, Connolly MJ. Axillary sweating in clinical lality as a marker of hydration status. Med Sci Sports Exerc 2011;43:
assessment of dehydration in ill elderly patients. BMJ 1994;308:1271. 1080e1084.
19. Rowat A, Smith L, Graham C, et al. A pilot study to assess if urine specific 45. Perrier E, Demazieres A, Girard N, et al. Circadian variation and responsiveness
gravity and urine colour charts are useful indicators of dehydration in acute of hydration biomarkers to changes in daily water intake. Eur J Appl Physiol
stroke patients. J Adv Nurs 2011;67:1976e1983. 2013;113:2143e2151.