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DOI 10.1007/s00134-012-2691-0
Andreas S. Fazekas
Georg-Christian Funk
Daniela S. Klobassa
Horst Ruther
Ingrid Ziegler
Rolf Zander
Hans-Jurgen Semmelrock
ORIGINAL
Introduction
Osmolality is a measure of solute concentration, defined
as the number of osmotically active particles (osmoles)
per kilogram of water [1]. Osmolality of human plasma is
tightly regulated and averages at 288 5 mosmol/kg
H2O [2]. Serum or plasma osmolality can be measured by
Methods
Study population
The study was prospective and observational in nature.
Patients under the age of 17 years were excluded. No
additional interventions were undertaken and the analysis
was performed on anonymized left-over samples obtained
during clinical routine. The local ethics committee confirmed in writing that due to the nature of the study ethics
approval did not have to be sought. A patient mix was
chosen to reflect the clinical areas where measuring serum
osmolality is of the greatest clinical relevance.
Table 1 Overview of the equations for the calculation of osmolality. For each formula the units for the plasma constituents are
millimoles per litre.
Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21a
21ba
22
23
24
25
26
27
28
29
30
31
32
33
34
35
Formula
References
?
[9]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[22]
[4]
[23]
[24]
[25]
[26]
[26]
[27]
[28]
[28]
[29]
[30]
[31]
[32]
[3]
[3]
[33]
[34]
[34]
[35]
[6]
Data collection
Results
Patient characteristics
Active plasma constituents (as outlined in Laboratory
assays) were measured in anonymized samples from 41
outpatients and 195 acutely ill inpatients (total 236 adult
subjects) at a university hospital in Graz, Austria, between
1 July and 19 November 2010. The sex of 232 of the 236
subjects was known; 110 (47 %) were female. The age of
231 subjects was recorded (mean age 58 years, range
1788 years, SD 16 years). The patient mix according to
treating specialties is shown in Table 2.
Na? (mmol/l)
K? (mmol/l)
Ionized Ca (mmol/l)
Cl- (mmol/l)
Glucose (mmol/l)
Lactate- (mmol/l)
Urea (mmol/l)
pH
pCO2 (mmHg)
cHCO3- (mmol/l)
Base excess (mmol/l)
Colloid osmotic pressure
Outpatients
(mmHg)
Osmolality
(mosmol/kg H2O)
The normal values for the calculation of osmolality in
Mean
Standard
deviation
Range
141
3.54
0.99
101
5.8
1.9
6.7
7.367
46.6
25.7
-0.2
19.7
4
0.65
0.11
4
2.1
1.3
4.5
0.055
7.5
3.3
3.2
3.1
125152
2.005.00
0.001.00
77110
2.015.0
0.08.0
1.029.0
7.1987.529
31.077.0
16.044.0
-11.014.0
14.026.0
291
244320
Measured osmolality
Number
Outpatients
Anaesthesia
Surgery
Internal medicine
Neurosurgery
Unclassified
Total
41
15
25
113
33
9
236
17
6 osmolalities and the variance of the differences
11 between the two
48
14 With a regression coefficient of 0.046 (p = 0.01), the
4
Table 4 Results of the statistical evaluation of the 36 formulas in the overall cohort
Formula
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21a
21b
22
23
24
25
26
27
28
29
30
31
32
33
34
35
Calculated osmolality
Mean SD
Range
266.9
306.2
272.4
300.2
281.2
282.5
292.2
289.5
292.5
288.7
296.6
291.9
295.7
277.4
291.3
286.0
292.9
285.7
271.4
282.4
281.4
284.9
300.0
293.9
293.4
299.3
268.0
296.7
326.0
291.1
290.7
283.4
296.7
298.3
299.7
290.0
235.0290.0
263.0334.0
238.0297.0
261.0325.0
244.0304.0
250.0304.0
256.0318.0
257.0311.0
260.0314.0
255.0310.0
262.0319.0
256.0318.0
257.0320.0
243.0302.0
255.0317.0
251.0312.0
256.0319.0
248.0309.0
237.0291.0
248.0307.0
247.0306.0
249.0314.0
261.0324.0
255.0323.0
254.0321.0
263.0325.0
234.0293.0
271.0316.0
288.0356.0
256.0316.0
253.0314.0
244.0311.0
258.0327.0
259.0326.0
261.0331.0
253.0322.0
6.8
9.5
7.1
7.8
7.4
7.2
7.6
7.2
7.2
7.3
7.6
7.5
7.7
7.1
7.5
7.5
7.7
7.5
6.9
7.1
7.1
8.1
7.8
8.5
8.4
7.5
7.2
5.9
8.4
7.3
7.5
8.4
8.6
8.4
8.6
7.9
Discussion
We present a statistical evaluation of 36 published formulas for calculating plasma osmolality including
Zanders novel formula. Previous evidence-based data in
the field are scarce [8]. When judging the quality of the
above formulas, the feature of the highest clinical relevance in our opinion was the mean difference between
calculated and measured osmolality, here called bias 1.
We consider a mean difference of \2 mosmol/kg H2O as
desirable, with a value above 5 mosmol/kg H2O significantly compromising the usefulness of the formula, as an
observed difference of above 5 mosmol/kg H2O by definition would indicate the presence of an osmolal gap.
Only 9 out of the 36 formulas showed a mean difference
of \2 mosmol/kg H2O and only four formulas including
the novel formula showed mean differences of \1
mosmol/kg H2O. When comparing the three formulas with
the lowest mean differences (formulas 29, 30 and 35), the
Bias 2
Bias 3
Regression
coefficient
p value
Regression
coefficient
p value
0.345
-0.017
0.292
0.187
0.256
0.31
0.202
0.301
0.304
0.277
0.227
0.217
0.197
0.294
0.215
0.226
0.189
0.224
0.338
0.283
0.284
0.148
0.189
0.097
0.107
0.235
0.28
0.471
0.106
0.248
0.215
0.108
0.082
0.104
0.083
0.161
0.0001
0.782
0.0001
0.0001
0.0001
0.0001
0.0001
0.0001
0.0001
0.0001
0.0001
0.0001
0.0001
0.0001
0.0001
0.0001
0.0001
0.0001
0.0001
0.0001
0.0001
0.0001
0.0001
0.001
0.0001
0.0001
0.0001
0.0001
0.001
0.0001
0.0001
0.001
0.009
0.001
0.009
0.0001
0.01
-0.003
0.007
-0.006
-0.005
0.016
-0.011
0.015
0.004
0.018
-0.01
0.0000394
-0.007
0.008
0.001
-0.003
0
-0.005
0.001
0.013
0.013
0.022
-0.001
0.012
0.019
0.007
0.003
0.045
0.014
0.009
-0.007
0.026
0.01
0.019
0.012
0.046
0.687
0.937
0.797
0.806
0.836
0.674
0.688
0.688
0.912
0.633
0.792
0.999
0.754
0.754
0.968
0.919
0.99
0.834
0.967
0.615
0.628
0.294
0.962
0.528
0.322
0.789
0.889
0.081
0.525
0.734
0.776
0.215
0.608
0.309
0.571
0.01
References
1. US National Library of Medicine.
http://www.ncbi.nlm.nih.gov/
mesh?term=osmolality. Accessed on 10
Sept 2012
2. Zander R (2009) Fluid management,
2nd edn. Bibliomed, Melsungen,
Germany.
http://www.physioklin.de/fileadmin/
user_upload/literatur/z/
fluid_management_1109.pdf. Accessed
10 Sep 2012
3. Rasouli M, Kalantari KR (2005)
Comparison of methods for calculating
serum osmolality: multivariate linear
regression analysis. Clin Chem Lab
Med 43:635640
4. Glasser L, Sternglanz PD, Combie J,
Robinson A (1973) A serum osmolality
and its applicability to drug overdose.
Am J Clin Pathol 60:695699
5. Purssell RA, Lynd LD, Koga Y (2004)
The osmole gap as a screening test for
the presence of toxic substances: a
review of the literature. Toxicol Rev
23:189202
6. Zander R (2012) Optimale Berechnung
der Osmolalitat. Physioklin, Mainz.
http://www.physioklin.de/physiopoc/
saeure-basen-sauerstoff-elektrolytstatus/optimale-berechnung-derosmolalitaet.html. Accessed 10 Sep
2012
7. Bland JM, Altman DG (1999)
Measuring agreement in method
comparison studies. Stat Methods Med
Res 8:135160
8. Krahn J, Khajuria A (2011) Is osmol
gap an effective screen in accurate
prediction of toxic volatiles? Clin Lab
57:297303
9. Edelman IS, Leibman J, OMeara MP,
Birkenfeld LW (1958) Interrelations
between serum sodium concentration,
serum osmolarity, and total
exchangeable sodium, total
exchangeable potassium, and total body
water. J Clin Invest 37:12361256
10. Holmes JH (1962) Measurement of
osmolality in serum, urine and other
biologic fluids by the freezing point
determination. American Society of
Clinical Pathologists, Chicago, IL