Dextrose Saline Compared With Normal

Saline Rehydration of Hyperemesis

Gravidarum
A Randomized Controlled Trial
Peng Chiong Tan,

FRCOG,

Mat Jin Norazilah,

MD,

and Siti Zawiah Omar,

MOG

OBJECTIVE: To compare 5% dextrose0.9% saline

against 0.9% saline solution in the intravenous rehydration of hyperemesis gravidarum.

resolution of hyponatremia, hypochloremia and hypokalemia, length of hospitalization, duration of intravenous

antiemetic, and rehydration were not different.

METHODS: Women at their first hospitalization for

hyperemesis gravidarum were enrolled on admission to
the ward and randomly assigned to receive either 5%
dextrose0.9% saline or 0.9% saline by intravenous infusion at a rate 125 mL/h over 24 hours in a double-blind
trial. All participants also received thiamine and an antiemetic intravenously. Oral intake was allowed as tolerated. Primary outcomes were resolution of ketonuria and
well-being (by 10-point visual numerical rating scale) at
24 hours. Nausea visual numerical rating scale scores
were obtained every 8 hours for 24 hours.

CONCLUSIONS: Intravenous rehydration with 5%

dextrose0.9% saline or 0.9% saline solution in women
hospitalized for hyperemesis gravidarum produced
similar outcomes.

RESULTS: Persistent ketonuria rates after the 24-hour

study period were 10 of 101 (9.9%) compared with 11 of
101 (10.9%) (P..99; relative risk 0.9, 95% confidence
interval 0.42.2) and median (interquartile range) wellbeing scores at 24 hours were 9 (810) compared with
9 (89.5) (P5.73) in the 5% dextrose0.9% saline and 0.9%
saline arms, respectively. Repeated measures analysis of
variance of the nausea visual numerical rating scale score
as assessed every 8 hours during the 24-hour study
period showed a significant difference in favor of the
5% dextrose-0.9% saline arm (P5.046) with the superiority apparent at 8 and 16 hours, but the advantage had
dissipated by 24 hours. Secondary outcomes of vomiting,
From the Department of Obstetrics and Gynaecology, University of Malaya,
Lembah Pantai, Kuala Lumpur, Malaysia.
Funded by the University of Malaya, Grant RG412/12HTM.
Corresponding author: Peng Chiong Tan, FRCOG, Department of Obstetrics
and Gynaecology, University of Malaya, Lembah Pantai, Kuala Lumpur 50603,
Malaysia; e-mail: pctan@um.edu.my.
Financial Disclosure
The authors did not report any potential conflicts of interest.
2013 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins.
ISSN: 0029-7844/13

VOL. 121, NO. 2, PART 1, FEBRUARY 2013

CLINICAL TRIAL REGISTRATION: ISRCTN Register,

www.controlled-trials.com/isrctn, ISRCTN65014409.
(Obstet Gynecol 2013;121:2918)
DOI: http://10.1097/AOG.0b013e31827c5e99

LEVEL OF EVIDENCE: I

yperemesis gravidarum has for practical purposes

been defined as intractable vomiting of pregnancy
severe enough to require hospital admission1 affecting
up to 2.3% of pregnancies.2 Hyperemesis gravidarum
is thus differentiated from the less severe nausea and
vomiting of pregnancy, which affects up to 85% of
pregnancies.3 Hyperemesis gravidarum is the second
most common indication for hospitalization in women
with successful pregnancies.4 Patients affected by
hyperemesis gravidarum are dehydrated and starved
with associated metabolic, electrolyte, and endocrine
disturbances: hyponatremia is present in 4349% and
hypochloremia in 3340% on hospital admission.5,6
Ketonemia and resultant ketonuria is the consequence
of the switch to an alternative energy source when
dietary glucose is insufficient for metabolic needs.7
The brain in the satiated state uses glucose as the exclusive energy substrate.8 The average requirement by the
adult brain for glucose is 100 g per day and the recommended daily amount for glucose in pregnancy is
175 g.9 Adults should get 4565% of their calories from
carbohydrates and young women in the first trimester
of pregnancy should consume 2,400 calories per day.9

OBSTETRICS & GYNECOLOGY

291

Approximately 25% of patients with hyperemesis gravidarum treated with metoclopramide and standard
saline rehydration were still ketonuric at 24 hours.10
Our objective was to estimate whether the addition
of 5% dextrose to 0.9% saline rehydration solution in
the first 24 hours after hospitalization, thereby providing 150 g of glucose over 24 hours intravenously
(equivalent to 600 calories) when nutritional intake is
likely still limited, would result in faster resolution of
ketonuria and a more rapid general recovery, culminating in increased perception of well-being.

PATIENTS AND METHODS

The trial was conducted in a university hospital in
Kuala Lumpur, Malaysia. Ethical oversight was provided by the University of Malaya Medical Center
Medical Ethics Committee (approval date September
22, 2010, reference number 811.8). This trial was
performed in compliance with the Declaration of
Helsinki. The trial is registered with a public trial
registry with the identifier ISRCTN65014409. All
participants provided informed written consent.
Women at their first hospitalization for hyperemesis gravidarum (intractable nausea and vomiting
of pregnancy with dehydration and starvation clinically
judged to require hospitalization for intravenous
rehydration and antiemetic drug administration) were
enrolled within 2 hours of ward admission by their
health care providers and randomly assigned to receive
either 5% dextrose0.9% saline or 0.9% saline by intravenous infusion at a rate 125 mL/h over 24 hours in
a double-blind trial. Women already under intravenous
rehydration therapy were not recruited. We did not
provide outpatient intravenous rehydration and antiemetic therapy for hyperemesis gravidarum; women
who needed these therapies were all admitted. Other
inclusion criteria were age 18 years or older, ketonuria
by urine dipstick of at least 1+ on admission, gestation
16 weeks or less, plasma glucose 110 mg/dL or less,
and sodium 125 mmol/L or greater on admission.
We excluded women in the case group with
multiple gestation, established nonviable pregnancy,
pre-existing medical conditions that can cause nausea
and vomiting (eg, culture-proven symptomatic urinary
tract infection, dengue fever), gastrointestinal causes of
vomiting (eg, gastroenteritis, gastritis, peptic ulcer),
medical causes of vomiting (eg, diabetic ketoacidosis),
and women with underlying medical problems (eg,
established gestational hypertension, diabetes, heart
disease, renal disease, and thyroid disorder).
In our center, as standard initial treatment, patients
with hyperemesis gravidarum received intravenous
rehydration with 0.9% saline solution (potassium

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Tan et al

Rehydration in Hyperemesis Gravidarum

chloride was added as required if hypokalemic), 10 mg

oral thiamine daily, and an intravenous antiemetic
(typically 10 mg metoclopramide 8 hourly).11 Oral
intake was allowed as tolerated at a pace decided by
the affected women. We did not ask participants to
record their oral intake.
Participants were recruited by health care providers as they were admitted to the gynecology ward.
Blood was taken for renal function, plasma glucose,
and full blood count. They also were given the visual
numerical rating scale for nausea to be filled out at
recruitment and 8, 16, and 24 hours after admission.
Randomization was affected by the sequential
opening of numbered, sealed, opaque envelopes stating
Protocol A or Protocol B. Randomization sequence
on a one-to-one ratio was computer-generated (using
http://www.random.org) for 223 participants by a coauthor (P.C.T.) who played no role in enrollment.
Intravenous solutions were prepared by a coauthor
(M.J.N.) using standard hospital issue 5% dextrose
0.9% saline or 0.9% saline solution in 500-mL containers with the manufacturers label stripped off
and relabeled as solutions A or B. The solutions and
containers were identical in appearance except for the
A or B labels. Randomization was to either A or B
(either 63500 mL .9% saline or 63500 mL of 5%
dextrose0.9% saline) to be given intravenously over
24 hours (ie, 500 mL of solution every 4 hours). One
gram (9.5 mmol) of potassium chloride can be added
to each 500-mL solution as required to correct hypokalemia. Participants and health care providers were
thus both blinded to the allocated solution.
A multivitamin preparation, P-Trovite, which
contains 250 mg thiamine, was given intravenously
to all participants before starting the trial rehydration
solution to prevent Wernickes encephalopathy that
may arise as a consequence of dextrose infusion in
a severely thiamine-deficient state. Intravenous antiemetic was also prescribed according to health care
providers to all participants for 24 hours or until significant symptom relief was established.
During the 24-hour study period, urine was
checked by dipstick 8 hourly for ketonuria and
glycosuria. If there was significant glycosuria 2+ or
greater present, the patients capillary glucose level
was checked with a glucometer and if reading
8 mmol/L or greater, infusion fluid was to be changed
to open-label standard 0.9% saline. Participants were
instructed to mark the nausea visual numerical rating
scale (10 points, high score denoting more severe nausea) before initial administration of the intravenous
fluid regime and then at 8, 16, and 24 hours. At
24 hours, participants were also asked to mark their

OBSTETRICS & GYNECOLOGY

with the Fishers exact test and larger categorical data

sets with the x2 test; ordinal data and nonnormally
distributed continuous data were analyzed with the
Mann-Whitney U test. A repeated-measures analysis
of variance was applied to the nausea visual numerical
rating scale scores and to ketonuria status. All tests
were two-sided and P,.05 was considered significant.

perceived well-being over the study period with a

10-point visual numerical rating scale (higher score,
greater well-being). At the conclusion of the 24-hour
main study period, open-label intravenous fluid was
started if still required.
Primary outcomes were resolution of ketonuria and
well-being (by 10-point visual numerical rating scale) at
24 hours. Secondary outcomes included frequency of
vomiting in the 24-hour study period; nausea visual
numerical rating scale at 8, 16, and 24 hours, hyponatremia (135 mmol/L or less); hypokalemia (3.5 mmol/L
or less); hypochloremia (99 mmol/L or less); hyperglycemia (8 mmol/L or greater) at the end of the 24-hour
main study period; duration of intravenous antiemetic
and intravenous rehydration during hospitalization;
and the hospital admission to discharge interval.
Data were extracted onto the case report form after
hospital discharge from case notes, laboratory reports,
and direct contact of participants if needed.
There is no trial comparing intravenous fluid
regimes for hyperemesis gravidarum to guide sample
size calculation. A previous trial of promethazine
compared with metoclopramide (using 0.9% saline
as the standard intravenous fluid) in our center has
shown that 25% of patients with hyperemesis gravidarum had not cleared their ketonuria and well-being
by visual numerical rating scale is 7.662.2 in the
metoclopramide arm at 24 hours.10 Sample size calculations were made with the PS program. Assuming a
10% compared with 25% (relative risk 0.4) rates for
persistence of ketonuria at 24 hours for 5% dextrose
0.9% saline and 0.9% saline arms respectively,
a5.05, power 80%, one-to-one recruitment ratio,
and applying the x2 test, 100 women are required in
each arm. Factoring in a 10% dropout rate, a total
of (200/0.9) 223 women are needed for a suitably
powered study. Similarly, assuming that well-being
visual numerical rating scale score will improve by 1
with 5% dextrose0.9% saline, applying the Students
t test, 77 participants will be required in each arm. If
the Mann-Whitney U test were to be applied instead
of the Students t test in the event of nonnormally
distributed visual numerical rating scale scores, a
10% increase in numbers is appropriate and factoring
in a 10% dropout rate, a total of only (15431.1/0.9)
189 women are required for a powered study on this
outcome. We planned to recruit 223 women.
Data were entered into SPSS 17. Analysis was by
intention to treat after exclusions for criteria infringements. Normality of data distribution was checked
with the Kolmogorov-Smirnov test. Normally distributed continuous data were analyzed with the Students
t test. Two-by-two categorical data sets were analyzed

The trial was conducted from November 9, 2010, to

February 6, 2012. Recruitment was stopped on reaching the targeted number of participants. The recruitment flowchart of participants through the trial is
shown in Figure 1. Exclusions were mostly the result
of study criteria infringements (shown in Fig. 1) that
were ascertained only after randomization as a result
of our pragmatic trial process where allocated treatment
was started before full test results were available. All
participants received P-Trovite intravenously and had
their rehydration regimen administered as allocated.
The characteristics of the participants in the two
trial arms are shown in Table 1. Participants in the two
arms have similar characteristics except for mean
serum potassium in which there was a mean difference of 0.1 mmol/L between the trial arms. All other
parameters from the standard renal function test, full
blood count, and random glucose as well as biometric
variables of blood pressure and pulse at recruitment
were similar (result not shown).
Table 2 displays the primary outcomes of ketonuria and well-being visual numerical rating scale score
according to treatment allocation. Ketonuria was still
present at 24 hours in 10 of 101 (9.9%) compared with
11 of 101 (10.9%) (P,.99) (relative risk 0.9, 95% confidence interval [CI 0.42.2) and median (interquartile
range) well-being score was 9 (810) compared with 9
(89.5) (P5.73) for 5% dextrose0.9% saline and 0.9%
saline arms, respectively, at the end of the 24-hour
main study period.
Of the secondary outcomes (Table 3), the nausea
visual numerical rating scale scores at 8 and 16 hours
showed a significant reduction (P,.01 and P5.03,
respectively) in favor of the 5% dextrose0.9% saline
arm but the difference had dissipated by 24 hours.
Repeated-measures analysis of variance of betweensubject nausea visual numerical rating scale scores
showed a significant result (P5.046), but interaction
of treatment and time was also significant (P5.004).
Hospital stays (defined as interval in hours from randomization to documented medical decision to discharge) were 43621 compared with 48621 (P5.14)
for 5% dextrose0.9% saline and 0.9% saline arms,
respectively.

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Tan et al

RESULTS

Rehydration in Hyperemesis Gravidarum

293

Hospitalizations for presumed

hyperemesis gravidarum
N=422
Rehopsitalizations
n=68
Women potentially eligible
for trial entry
n=354

Randomization
envelope opened
n=223

Women recruited
n=222

Randomized to dextrose-saline
n=111

Envelope mistakenly opened

and discarded (randomization
to dextrose saline)
n=1

Randomized to normal saline

n=111
Participant withdrawal
n=1

Participant withdrawal
n=2
Enrollment criteria infringement: n=7
Urinary tract infections: 2
High blood glucose: 2
Gestational age greater
than 16 weeks: 1
Rehospitalization: 2
Available for analysis
as per enrollment criteria
n=102

Not approached or
declined participation
n=131

Enrollment criteria infringement: n=9

Urinary tract infections: 2
High blood glucose: 5
Gestational age greater
than 16 weeks: 1
Multiple pregnancy: 1
Available for analysis
as per enrollment criteria
n=101

Fig. 1. Recruitment flowchart for a double-blind randomized trial of intravenous rehydration with 5% dextrose0.9% saline
compared with 0.9% saline solution at the first hospitalization for hyperemesis gravidarum.
Tan. Rehydration in Hyperemesis Gravidarum. Obstet Gynecol 2013.

There was a statistically significant difference in

the serum potassium level after completion of the 24hour study period (mean6standard deviation): 3.96.4
compared with 3.86.3 mmol/L (5% dextrose0.9%
saline compared with 0.9% saline arms; P5.04);
the mean .1-mmol/L difference in serum potassium
level is identical to the pretreatment mean difference
between the two trial arms and is likely to have arisen
from the differing baseline. The proportion classified
as hypokalemic (3.5 mmol/L or less) was not different
(19.1% compared with 28.7%; P5.17, relative risk .6,
95% CI 0.31.2 between the trial arms at 24 hours.
Post hoc, using the paired t test, for the entire trial
cohort, mean glucose, serum sodium, and chloride
levels increased in the first 24 hours after hospitalization (87100 mg/dL, 134138, 101106 mmol/L
respectively, all P,.001), whereas that for serum
potassium decreased marginally from 3.92 to 3.84
mmol/L (P5.014). Adjusting for antiemetic regimen
did not alter the result for persistence of ketonuria

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Rehydration in Hyperemesis Gravidarum

at 24 hours (adjusted odds ratio 0.8, 95% CI

0.32.0, P5.60; 5% dextrose0.9% saline compared
with 0.9% saline). Restricting analysis to only the
metoclopramide-exposed cases also did not alter the
nonsignificant results on persistence of ketonuria
(P5.81) and well-being score (P5.43); the significant
result on the nausea visual numerical rating scale by
repeated-measures analysis of variance (P5.049) in
favor of the 5% dextrose0.9% saline arm remained.
If participants excluded postrandomization as
a result of enrollment criteria infringements were
included in the analysis, outcomes between the trial
arms were still similar. Similarly, adjusting for the
potassium level also did not materially alter the
results. There was no protocol curtailment as a result
of hyperglycemia during the 24-hour study period.

DISCUSSION
To our knowledge, intravenous rehydration
regimes in the management of hyperemesis

OBSTETRICS & GYNECOLOGY

Table 1. Characteristics of All Trial Participants According to Randomization to 5% Dextrose0.9% Saline

or Normal Saline Solution for Rehydration of Hospitalized Hyperemesis Gravidarum Cases
Characteristic

Dextrose Saline (n5111)

Normal Saline (n5111)

28.564.6
9.862.8
0 (02)
15 (13.5)

29.364.6
9.862.5
1 (02)
16 (14.4)

.22
.95
.90
..99
.25

85 (76.6)
11 (9.9)
15 (13.5)

85 (76.6)
17 (15.3)
9 (8.1)

85 (76.6)
85 (76.6)

26 (23.4)
26 (23.40

6 (5.4)
45 (40.5)
60 (54.1)
58.2612.2
24.064.5

2 (1.8)
51 (45.9)
58 (523)
57.3611.4
23.764.5

11 (9.9)
14 (12.5)
23 (20.7)
63 (56.8)
13562
80 (72.1)
4.060.4
14 (12.6)
10262
20 (18.0)
89611
0.3860.03
9 (710)

12 (10.8)
13 (11.7)
27 (24.3)
59 (53.2)
13462
84 (75.7)
3.960.4
22 (19.8)
10163
29 (26.1)
89616
0.3860.03
9 (710)

94 (85.5)
11 (10.0)
5 (4.5)
5.763.4
55/92 (59.8)

79 (72.5)
18 (16.5)
12 (11.0)
5.663.2
54/94 (57.4)

Age (y)
Gestation (wk)
Parity
Prior miscarriage
Ethnicity
Malay
Indian
Other
Employment
Employed
Homemaker or student
Education
Primary
Secondary
Tertiary
Weight (kg)
Body mass index (kg/m2)
Ketonuria (dipstick)
1+
2+
3+
4+
Serum sodium (mmol/L)
Hyponatremia (135 mmol/L or less)
Serum potassium (mmol/L)
Hypokalemia (3.5 mmol/L or less)
Serum chloride (mmol/L)
Hypochloremia (99 mmol/L or less)
Plasma glucose (mg/dL)
Hematocrit
Nausea score*
Antiemetic regimen
Metoclopramide
Prochlorperazine
Ondansetron
Weight loss percentage (n5186)
Weight loss 5% or greater

..99
.30

.59
.65
.67

.12
.65
.03
.20
.07
.20
.67
.98
.39
.053

.83
.77

Data are mean6standard deviation, median (interquartile range), or n (%) unless otherwise specified.
Analysis by Students t test for continuous variables, Mann-Whitney U test for ordinal data, Fishers exact test for 232 categorical data sets,
and x2 test for larger than 232 categorical data sets. All statistical tests are two-sided.
* Nausea is self-scored by participants using a 10-point numeric rating score, with a score of 110 as nausea increases.

Weight loss defined as (prepregnancy weightcurrent weight)/prepregnancy weight3100all in kilograms; prepregnancy weight as
reported by participants where available; n,203 as a result of incomplete data ascertainment.

gravidarum have not been previously studied. We

performed an unrestricted online PubMed search
(http://www.ncbi.nlm.nih.gov/sites/entrez) on May
13, 2012, using the search terms hyperemesis gravidarum hydration trial and identified only a review
article. There seems to be little change since the 2004
Practice Bulletin from the American College of
Obstetricians and Gynecologists, which stated that
no study has compared different fluid replacements
for nausea and vomiting of pregnancy.3
Intravenous rehydration is a mainstay of management in hyperemesis gravidarum, but reflecting

the dearth of evidence, the fluid regime is typically not

defined in guidance and reviews.3,12,13 A recent review
cautions against the use of dextrose in the rehydration
fluid in the rare event of Wernickes encephalopathy
being precipitated as a result of thiamine deficiency
and the overrapid correction of hyponatremia possibly leading to central pontine myelinolysis,14 whereas
another recommends total food avoidance and parenteral administration of carbohydrate, vitamins, and
amino acids in the process of correcting volume and
electrolyte imbalances in hyperemesis gravidarum.15
Our data suggested that intravenous multivitamins,

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Rehydration in Hyperemesis Gravidarum

295

Table 2. Primary Outcomes of 5% Dextrose0.9% Saline Compared With Normal Saline as Intravenous
Rehydration Solution for Hyperemesis Gravidarum
Dextrose Saline (n5102)

Normal Saline (n5101)

9 (810)
8.561.6
10 (9.9)

9 (89.5)
8.461.5
11 (10.9)

.73
.75
..99
.86

0
11
11
21
59

(0.0)
(10.8)
(10.8)
(20.6)
(57.8)

0
10
10
26
55

(0.0)
(9.9)
(9.9)
(25.7)
(54.5)

24
26
19
28
5

(23.5)
(25.5)
(18.6)
(27.5)
(4.9)

28
15
23
34
1

(27.7)
(14.9)
(22.8)
(33.70)
(1.0)

68
16
10
7

(67.3)
(15.8)
(9.9)
(6.9)

67
12
12
10

(66.3)
(11.9)
(11.9)
(9.9)

Well-being score at 24 h*
Persistent ketonuria at 24 h
Ketonuria at enrollment
0
1+
2+
3+
4+
Ketonuria at 8 h
0
1+
2+
3+
4+
Ketonuria at 16 h
0
1+
2+
3+
Ketonuria at 24 h
0
1+
2+
3+
Repeated measures analysis of variance

Relative Risk (95% CI)

0.9 (0.42.2)

.14

.73

.42
91 (90.1)
90 (89.1)
8 (7.9)
5 (5.0)
1 (1.0)
4 (4.0)
1 (1.0)
2 (2.0)
of ketonuria status (between-patient effects)

.77

CI, confidence interval.

Data are median (interquartile range), mean6standard deviation, or n (%) unless otherwise specified.
Analysis by Mann-Whitney U test for ordinal data, Fishers exact test for 232 categorical data, set and x2 test for larger than 232 categorical
data sets. All statistical tests are two-sided.
* Well-being is assessed using a 10-point (110) visual numerical rating scale; higher score greater well-being.

antiemetic, and a rehydration regime comprising 3 L

of 0.9% saline over a 24-hour period in the initial
management of hyperemesis gravidarum is seemingly
effective: at 24 hours, in 89%. ketonuria had resolved,
hyponatremia reduced from 76% to 18% (with only
a single case of a 11-mmol/L increase in serum sodium
and another case in which serum sodium level peaked
outside our upper normal limit of 144 at 145 mmol/L),
nausea visual numerical rating scale reduced from
a median score of 9 to 2, and 54% (54 of 101) had
stopped vomiting altogether.
In the context of pediatric acute gastroenteritis,
intravenous dextrose in the rehydration fluid on an
outpatient basis reduced the risk of a return visit
requiring admission.16 It has been postulated that
reduced carbohydrate intake leads to free fatty acid
breakdown, excess ketones, and an increased likelihood
for continued nausea and vomiting and that the addition
of dextrose to intravenous rehydration therapy reduced
free fatty acid breakdown and reduced the incidence of
outpatient treatment failure as a result of intractable
nausea and vomiting.17 Our data showed a temporary

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Rehydration in Hyperemesis Gravidarum

reduction in nausea score in the 5% dextrose0.9%

saline arm at 8 and 16 hours, but the reduction did
not seem to be mediated through a reduction in ketonuria nor was there any reduction in vomiting.
Our trial protocol did not routinely include
potassium supplementation in the rehydration solution in either trial arm, although potassium could be
added to correct hypokalemia at health care providers instruction. This resulted in a marginal drop of
0.1 mmol/L in mean serum potassium level and an
increase in the proportion classified as hypokalemic
(3.5 mmol/L or less) from 17% to 24% (the lowest
recorded serum potassium of 3.0 mmol/L in one
woman) at 24 hours. In 51% of participants, serum
potassium level fell in the first 24 hours. There seems
to be a reasonable case for routine supplementary
potassium in the initial management of a typical case
of hyperemesis gravidarum.
There was a small 0.1-mmol/L difference in the
mean serum potassium level at recruitment and
similarly at end of the 24-hour study period between
the trial arms. The small difference at recruitment was

OBSTETRICS & GYNECOLOGY

Table 3. Secondary Outcomes of Randomized Trial of 5% Dextrose0.9% Saline Compared With Normal
Saline as Intravenous Rehydration Solution for Hyperemesis Gravidarum

Vomiting episodes*
Nausea score at enrollment
Nausea score at 8 h
Nausea score at 16 h
Nausea score at 24 h
Repeated-measures analysis of variance of
nausea score (between-patient effects)
Blood results at 24 h
Serum sodium (mmol/L)*
Hyponatremia (135 mmol/L or less)*
Serum potassium (mmol/L)*
Hypokalemia (3.5 mmol/L or less)*
Serum chloride (mmol/L)*
Hypochloremia (99 mmol/L or less)*
Plasma glucose (mg/dL)*
Hyperglycemia (145 mg/dL or greater)*
Duration of intravenous antiemetic use (h)
Duration of intravenous rehydration (h)
Recording of first oral intake (h after recruitment)
Oral intake by 8 h
Oral intake by 16 h
Oral intake by 24 h
Hospital stay (h)jj

Dextrose Saline
(n5102)

Normal Saline
(n5101)

0 (02)
9 (710)
6 (47)
4 (25)
2 (14)

0 (02)
9 (710)
7 (58)
5 (36)
2 (24)

13862
13 (13.8)
3.960.4
18 (19.1)
10663
1 (1.1)
100624
3 (3.0)
24617
33614
11.265.7
40/101 (39.6)
84/101 (83.2)
98/101 (97.0)
43621

13762
17 (18.1)
3.860.3
27 (28.7)
10564
5 (5.3)
100618
2 (2.0)
25615
37615
13.266.0
24/99 (24.2)
78/99 (78.8)
93/99 (93.9)
48621

Relative Risk
(95% CI)

.66
.45
,.01
.03
.39
.046

.55
.04
.17
,.01
.21
.97
.68
.61
.15
.022
.023
.47
.33
.14

0.7 (0.31.6)
0.6 (0.31.2)
0.2 (0.021.7)
1.5 (0.39.4)

2.0 (1.13.8)
1.3 (0.72.7)
2.1 (0.58.7)

CI, confidence interval.

Data are mean6standard deviation, median (interquartile range), or n (%) unless otherwise specified.
Analysis by Students t test for continuous variables. Mann-Whitney U test for ordinal data, Fishers exact test for 232 categorical data sets,
and x2 test for larger than 232 categorical data sets. All statistical tests are two-sided.
* Assessed at the end of the 24-hour study period.

Nausea is assessed using a 10-point (110) visual numerical rating scale: higher score signifies more nausea.

Over the entire course of the hospital stay.

Oral intake of solids or fluids of any quantity as first recorded by nurses or doctors; n,203 as a result of incomplete data ascertainment.
jj
Interval from recruitment to documented medical decision to discharge.

probably a chance occurrence, which was carried

through to the end of the study period. A 0.1-mmol/L
difference in mean serum potassium is unlikely to be
of clinical significance. Adjustment for potassium
level at recruitment did not affect primary outcome
of persistence of ketonuria between trial arms.
Despite 150 g of dextrose by intravenous administration (equivalent to 50% of the daily normal
carbohydrate intake in an average diet and 600
calories) to women in the 5% dextrose0.9% saline
arm, the rise in plasma glucose was similar in magnitude at 24 hours when compared with the 0.9% saline
arm. This finding may reflect oral food intake near the
24-hour mark in the 0.9% saline arm because nausea
and vomiting improved or increased glucose metabolism in the 5% dextrose0.9% saline arm driven by
availability. We did not ask the participants to document oral intake in this trial.
This trial has limitations and strengths. In the
0.9% saline arm, the persistent ketonuria rate was only

11% compared with an anticipated 25% as assumed in

the sample size calculation using earlier data.10 This
would have reduced the trials power to demonstrate
a difference. The improved ketonuria resolution rate
in the 0.9% saline arm of our current trial may be the
result of the routine use of P-Trovite multivitamin
supplement or a more rigorous and consistent perprotocol administration of the prescribed intravenous
rehydration solutions. On the other hand, because the
standard deviation in the well-being visual numerical
rating scale was 1.5 (compared with a standard deviation of 2 used in sample size calculation), this would
have increased the power of the trial to detect a 1-point
increase in well-being visual numerical rating scale
score to 99.7%. We believe our finding is generalizable for similarly managed inpatient hyperemesis
gravidarum populations.
Dextrose saline solution was not superior to normal
saline solution in the initial intravenous rehydration of
women hospitalized for hyperemesis gravidarum on

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Rehydration in Hyperemesis Gravidarum

297

a range of outcomes. However, because of the theoretical concern of Wernickes encephalopathy with dextrose infusion when in a thiamine-deficient state,
normal saline may be a better choice.
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