Journal of Analytical Toxicology,Vol. 23, November/December1999
Impact of Water-Induced Diuresis on Excretion Profiles
of Ethanol, Urinary Creatinine, and Urinary Osmolality
P. Bendtsen 1 and A.W.
Jones2, *
IAIcohol and Drug Dependence Unit and 2Departmentof Forensic Toxicology, University Hospital, Link6ping, Sweden
[Abstract
This article reports the impact of diuresis on urinary excretion of
ethanol in seven healthy volunteers who drank 1000 mL of export
beer (44 g ethanol) in 30 min and, 120 rain later, ingested 500 or
1000 mL of water within 5 min. Urine was voided before drinking
started and every 30-60 rain for 360 rain after the start of
drinking. The concentration of ethanol in urine (UAC) was
determined by headspace gas chromatography, the creatinine
content was determined by Jaffe's method, and osmolality was
measured by freezing point depression. Maximum diuresis
coincided with the peak UAC and was reached 60-90 min after
the end of drinking. The urinary creatinine and osmolality dropped
appreciably after drinking beer, and the lowest values coincided
with peak diuresis. Creatinine was < 0.2 g/L in 22% of urine
specimens, and osmolality was < 200 mOsm/kg in 31% of
specimens. Production of urine decreased as UAC entered the
postabsorptive phase but increased again after the subjects drank
water 120 min after alcohol consumption. The amount of ethanol
recovered in urine was 681 mg (standard deviation [SD] 203 rag)
corresponding to 1.5% (SD 0.46%) of the dose administered. The
concentrations of ethanol in successive voids during the
postabsorptive phase were not influenced after subjects drank 500
or 1000 mL of water although diuresis increased and urinary
creatinine and osmolality decreased. Measuring UAC provides a
reliable way to monitor recent drinking, and unlike the analysis of
illicit drugs in urine, the concentrations of ethanol are not
influenced by diuresis.
Introduction
Measuring the concentration of ethanol in urine presents no
analytical difficulties, and with the aid of gas chromatographic
(GC) or imrnunoassay methods, accurate and precise results
are obtained (1-5). However, care is necessary when the concentrations of ethanol in urine are interpreted, especially if the
aim is to estimate the person's co-existing blood-ethanol concentration (BAC) or to furnish evidence of alcohol-induced
* Author to whom correspondence should be addressed. Dr. A.W. Jones, Dept. of Forensic
Toxicology, University Hospital, 581 85 Link6ping, Sweden. Email [email protected].
impairment (6,7). Some of the difficulties interpreting UAC,at
least in part, stem from an erroneous comparison of the pharmacokinetics of ethanol with aspects of urine testing for illicit
drugs of abuse (8-10).
The aim of this study was to investigate the influence of
drinking water during the postabsorptive phase of ethanol
pharmacokinetics on the excretion profile of ethanol and on
the associated changes in urinary creatinine and osmolality,
both of which are widely used markers for highly dilute specimens (11). The magnitude of ethanol-induced and water-induced diuresis was determined along with the fraction of the
dose of ethanol recovered in the urine.
Material and Methods
Healthy male (n = 5) and female (n = 2) volunteers, all social
drinkers, with a mean age of 36 years (standard deviation [SD]
11 years) and mean body weight of 80 kg (SD 10 kg), participated in a controlled experiment. In two male subjects, the experiment was repeated twice to investigate within-subject
reproducibility. The study protocol was approved by the ethical
review committee at the University Hospital in Link6ping, and
the subjects gave verbal consent.
All participants were required to abstain from drinking alcohol for 24 h before the experiment began, and alcohol-free
status was confirmed by breath-alcohol analysis with an Alcolmeter S-D2 instrument (Lion Laboratories, Barry, Wales, U.K.).
After making an initial urinary void, the subjects were required
to consume 1000 mL of export beer (44 g ethanol), corresponding to 0.55 g ethanol per kilogram mean body weight, in
exactly 30 rain. Specimens of urine were then voided at 30, 60,
90, 120, 150, 180, 210, 240, 300, and 360 rain after finishing the
beer. The subjects were encouraged to empty the bladder completely each time urine was voided. The specimens were collected into a measuring cylinder, and the volumes were
recorded to the nearest 2 mL. At 120 rain postdrinking (150 min
from start), the subjects were required to drink either 500 or
1000 mL of tap water, and urine specimens were again collected at exactly timed intervals as indicated.
Reproduction(photocopying)of editorialcontentof thisjournalis prohibitedwithoutpublisher'spermission.
565
Journal of Analytical Toxicology, Vol. 23, November/December 1999
The concentration of ethanol in urine was determined by
headspace GC, which had a limit of detection of 0.01 g/L (12).
Urinary creatinine was determined by the Jaffe method on a Hitachi 717 analyzer (13), and osmolality was measured at the
hospital clinical chemistry laboratory by a method based on depression of the freezing point (14). Concentration-time profiles
of ethanol as well as changes in creatinine and osmolality were
plotted for each subject, and average curves and between-subject variation were calculated. The amount of ethanol excreted
in urine was determined as the product of concentration and
volume voided at each sampling time. Diuresis was reported as
the volume of urine produced per minute at each sampling
time.
Results
Figure 1 presents an example of the concentration-time profiles of ethanol in urine, the magnitude of diuresis, and changes
in urinary creatinine and osrnolality in one male subject considered representative of the group. Figure 2 shows the average
curves for all seven subjects.
These graphs show that the concentration of ethanol in
1000 mL beer
urine increased fairly rapidly after drinking the beer with a
mean peak UACof 0.70 g/L (SD 0.16 g/L) and a range from 0.51
to 0.98 g/L. The peak ethanol concentration was reached at 60
rain after the end of drinking the alcohol or 90 min after the
start of drinking. Ethanol-induced diuresis was most pronounced during the absorption portions of the curves with a
mean of 11.4 mL/min (SD 4 mL/min) and ranging from 4.7 to
16.6 mL/min. After the peak UACwas reached, the production
of urine decreased until the subjects drank water at 150 rain
timed from start of drinking. The maximum water-induced
diuresis was 4.7 mL/min (range 0.66-6.8 mL/min) and occurred at 60 min after the drink was finished. Water-induced
diuresis was less pronounced than alcohol-induced diuresis.
The total quantity of alcohol recovered in the urine was only
681 mg (SD 203 rag), corresponding to 1.5% (SD 0.46%) of the
44 g administered.
The shape of the excretion profile of ethanol during the
postabsorptive phase from 150 rain after drinking and later was
hardly influenced at all after the subjects drank 500 or 1000 mL
of water (Figures 1 and 2). Despite the increased volume of
urine produced, the concentration-time course of ethanol in
five successive voids after drinking the water remained on the
decline expected for zero-order elimination kinetics of ethanol.
The creatinine content of urine and the osmolality decreased
[
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Figure1. Urine-alcohol profile and diuresis (lower plot)in a male subject
who drank 1000 mL of beer (44 g ethanol) in 30 min and then ingested
500 mL of tap water 120 min later. The corresponding changes in urinary
creatinine and osmolality are shown in the upper plot.
566
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Figure 2. Mean curves (_+SD) for seven subjects after they drank 1000 mL
beer (44 g ethanol) in 30 min and then 500 or 1000 mL of tap water 120
rain later. The upper plot shows the time course of urinary creatinine and
osmolality and the lower plot the corresponding urinary alcohol profile
and diuresis.
Journal of Analytical Toxicology, Vol. 23, November/December1999
abruptly after the subjects drank beer, thereafter increasing
again before the subjects drank water at 150 rain (Figures 1
and 2). Figure 3 shows that creatinine content of urine and osmolality were highly correlated (r = 0.86, p < 0.001). Moreover,
urinary creatinine and osmolality decreased exponentially as
diuresis increased (Figure 4). The creatinine content of urine
was < 0.20 g/L in 22% of specimens, and osmolality was < 200
mOsm/kg in 31% of specimens.
(TBW) after the absorption process is complete. Indeed,
ethanol dilution can be used to estimate TBW,and the results
agree well with is9
and anthropometric methods
(15). The production of urine increased appreciably after
drinking beer because of the combined influences of waterinduced and ethanol-induced diuresis, as expected. The
diuretic action of ethanol is caused by inhibition of the
secretion of antidiuretic hormone vasopressin from the posterior pituitary gland (16). The production of highly dilute
urine was confirmed by a sharp drop in both creatinine
content and osmolality, and a large number of specimens were
Discussion
below the threshold values accepted in urine-drug testing
programs to spot highly dilute specimens (11). The peak
After drinking beer, wine, or spirits, the ethanol contained
diuresis was observed at 90 min after starting to drink beer
in these beverages mixes completely with total body water
and seemed to coincide with the lowest creatinine and osmolality values.
The concentration of ethanol in urine was
highest
at 90 rain after the start of drinking,
i
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1
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being followed by a more or less rectilinear
1400. N = 9 0
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declining phase until all the alcohol was
1200
r = 0 . 8 6 3 (p < 0 . 0 0 1 )
.............
eliminated after 6-7 h. The elimination
profile of ethanol in urine seemed to follow
.
...... . 9 ..........
.
1000
a zero-order kinetics and the linear decline
in UAC when the postabsorptive phase was
.~, 800
....... 9 9" . , , ~ 9"
- ........
...-'"
....'"
well
established was not disrupted after the
....
. .............
subjects
consumed 500 or 1000 mL of water
~0
~ 600 -e......9 9 1 4"o=<l"
9
9
.........
~"
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...'"
9
150 min from start of drinking (7,15). Di400: .... 9 _t,~,/o
:'--Y"
uresis does not change the concentration of
: ..............
ethanol in urine even though creatinine content and osmolality were markedly reduced
after drinking water. This supports an early
O
' '
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i
9
I
9
observation
made by Widmark (17,18) and
0.0
0.5
1.0
1.5
2.0
2.5
3.0
confirms that ethanol is excreted by the
U-Creatinine (g/L)
kidney according to a passive diffusion proFigure 3. Associationbetween creatininecontent and osmolality of urine specimenscollected after
cess (19-22). The concentration of ethanol
subjects drank 1000 mL beer (44 g ethanol) and 500 or 1000 mL tap water 120 min later.
in freshly produced urine reflects the concentration in the water fraction of blood
flowing to the kidney, and this is not influ1200
,
,
,
4.0
,
,
,
enced by drinking 500 or 1000 mL of water
(17,18). The TBW is about 50-60% of body
3.5weight,
and the concentration of ethanol in
1000
'4
TBW
is
not markedly altered by intake of
3.0~
500-1000
mL of water. The kidneys cannot
._1
800
le
produce
ethanol
at a greater concentration
" ~ 2.5~
0
than that existing in the TBW (20,21).
.EE 600
The fact that only 1-2% of the dose of
ethanol
administered was recovered in the
1.s-,
-~ 400- l " t
urine confirms previous work on the disposition and fate of ethanol in the body (23). The
E
normal
production rate of urine in healthy
O 200- i " e . : . .
I
adults is about 30-60 mL/h (720-1440
9
9
mL/day), and even increasing this volume by
o.o1 v T-t-,. : . . .
0
drinking
copious amounts of water will have
o
1'o'1'5 20
0
5
10 15 20
a
minimal
effect on the total amount of
Diuresis (mL/min)
Diuresis (mL/min)
ethanol cleared by renal excretion. The difFigure 4. Associationbetween creatininecontentof urine and diuresis(right frame) and osmolality
ferences in concentrations of ethanol between
and diuresis(left frame)after subjectsdrank 1000 mL beer (44 g ethanol) and 500 or 1000 mL tap
blood and urine depend mostly on the relative
water 120 rain later.
water content of the specimens analyzed and
~
i
567
Journal of Analytical Toxicology,Vol. 23, November/December1999
also on the phase of ethanol metabolism when the samples are
taken (24,25). During the absorption phase shortly after the
end of drinking, the BAC tends to exceed UAC, but when no
more alcohol is consumed and equilibration of ethanol in all
body fluids is complete, the UACis, as expected, always higher
than BAC because urine contains about 20% more water than
an equal volume of whole blood (7,25). The UAC/BACratio of
ethanol for venous whole blood and freshly produced urine
without long periods of storage in the bladder should be approximately 1.20:1.
Because neither UAC nor BAC are seemingly lowered after
drinking 500-1000 mL water, the urine/blood ratios of ethanol
should also remain unchanged despite a markedwater-induced
diuresis. This is important to consider when the UAC/BACratio
of ethanol is used to derive information about the likely time
of consumption of alcohol in relation to sampling and also
whether a person's BACmight have been rising or falling sometime prior to sampling (6,7,25). Urine is available in large volumes without invasion of the body and is widely used in
analytical toxicology to monitor alcohol and drug abuse (26).
The possibility of lowering the concentrations of illicit drugs in
urine by drinking water prior to voiding is well known (27), but
this strategy will not influence the concentration of ethanol in
urine.
Several recent studies have explored the possibility of monitoring abstinence by the determination of ethanol in urine as
a way to detect relapse in alcoholic outpatients or control for
alcohol consumption in workplace accidents (28). Measuring
UAC in the first morning void can disclose whether a person
consumed alcohol the night before, and such information is
useful to check for compliance with abstinence in addiction
medicine (28,29). Alcohol testing has proved a useful complement to personal interviews about the patient's drinking habits.
The first urinary void collected from a suspected drunk driver
involved in a road traffic accident will furnish a way to determine what the person's BAC was at the time of the crash.
Surprisingly, this approach is not much used in traffic-law enforcement but would serve as a useful complement to back extrapolation of BAC.
In conclusion, measuring ethanol in urine has many applications in analytical toxicology and interpretation of urine resuits for ethanol is a lot easier than for other drugs of abuse.
The UAC provides a useful way to monitor abstinence during
rehabilitation programs for convicted drunk drivers and other
public health activities where alcohol abuse is involved. Unlike
urinalysis of many drugs of abuse (cannabis, amphetamine),
the concentration of ethanol in the urine is not influenced by
diuresis or the pH of the urine specimens. Drinking a large
volume of water before voiding will not dilute the concentration of ethanol.
Acknowledgment
This work was supported by a grant from the Swedish
National Board of Forensic Medicine.
568
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