Full text of DOI:10.1007/BF03019733

OBSTETRICAL A N D PEDIARTIC ANESTHESIA
185
Dexamethasone prophy-
laxis of nausea and
vomiting after epidural
morphine for post-
Cesarean analgesia
Jhi-Joung Wang MD DMSC,*†
Shung-Tai Ho MD MS,*
Chih-Shung Wong MD PhD,*
Jann-Inn Tzeng MD,‡
Hang-Seng Liu MD,§
Luo-Ping Ger RN MPH*
Purpose: To determine the minimum effective dose of dexamethasone in preventing nausea and vomiting asso-
ciated with epidural morphine for post-Cesarean analgesia.
Method: One hundred and eighty parturients (n=45 in each of four groups) requiring epidural morphine for
post-Cesarean analgesia were enrolled in this randomized, double-blinded, placebo-controlled study. At the end
of surgery, parturients received either dexamethasone, at doses of 10 mg, 5 mg, 2.5 mg, or saline iv. Three mil-
ligrams epidural morphine were given to all parturients for postoperative analgesia. The incidence of PONV and
side effects were estimated for 24 hr after delivery by blinded, trained nurse anesthetists.
Results: Parturients who received dexamethasone, either 10 mg or 5 mg were different from those who
received saline alone in the following parameters: the total incidence of nausea and vomiting, incidence of > 4
vomiting episodes, number the of parturients requiring rescue antiemetics, and the total number of parturients
with no vomiting and/or no antiemetic medication (P < 0.05 to P < 0.01 ). The differences between dexam-
ethasone 10 mg and 5 mg were not significant. Dexamethasone 2.5 mg was partially effective.
Conclusion: Dexamethasone, 5 mg iv, is suggested as the minimum effective dose in preventing nausea and
vomiting associated with epidural morphine for post-Cesarean analgesia.
Objectif : Déterminer la dose efficace minimale de dexaméthasone à utiliser pour prévenir les nausées et les
vomissements liés à l’administration épidurale de morphine comme analgésie post-césarienne.
Méthode : Cent quatre-vingt parturientes (n=45 dans chacun des quatre groupes), nécessitant une analgésie
épidurale post-césarienne avec morphine, ont participé à l’étude randomisée et à double insu contre placebo.
Elles ont reçu, à la fin de l’opération, soit 10 mg, 5 mg ou 2,5 mg de dexaméthasone, soit une solution salée iv.
Toutes ont reçu 3 mg de morphine comme analgésie postopératoire épidurale. L’incidence des NVPO et des
effets secondaires a été évaluée pendant vingt-quatre heures après l’accouchement par des infirmières impartiales
diplômées en anesthésie.
Résultats : Les parturientes qui ont reçu 10 mg ou 5 mg de dexaméthasone ont présenté des caractéristiques
différentes de celles qui ont reçu le placebo pour les paramètres suivants: l’incidence totale de nausées et de vo-
missements, l’incidence d’épisodes de vomissements > 4, le nombre de patientes qui ont eu besoin d’antiémé-
tiques de secours et le nombre total de parturientes sans vomissements et/ou sans médication antiémétique (P
< 0,05à P < 0,01 ). Aucune différence significative n’était liée aux doses de 10 mg et de 5 mg de dexamétha-
sone. La dexaméthasone à 2,5 mg n’a été que partiellement efficace.
Conclusion : La dexaméthasone, administrée en doses de 5 mg iv, est suggérée comme la dose efficace mini-
male pour prévenir les nausées et les vomissements associés à l’analgésie épidurale post-césarienne avec de la
morphine.
From the Department of Anesthesiology,* and Department of Obstetrics and Gynecology,§ Tri-Service General Hospital, National
Defense Medical Center, Taipei; the Department of Anesthesiology,† Chi-Mei Medical Center, Tainan; the Department of
Anesthesiology,‡ Municipal Women’s and Children’s General Hospital, Kaohsiung, Taiwan.
Address correspondence to: Dr. Jhi-Joung Wang, Department of Anesthesiology, Chi-Mei Medical Center, No. 901, Chung-Hwa Rd.,
Yung - Kang City, Tainan Hsien, Taiwan. Phone: 886-2-87927125; Fax: 886-2-87927130; E-mail: painlab@tpts5.seed.net.tw
The work was done in the Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Accepted for publication November 9, 2000.
CAN J ANESTH 2001 / 48: 2 / pp 185–190

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CANADIAN JOURNAL OF ANESTHESIA
PIDURAL morphine has a potent and
long-acting analgesic effect for postopera-
tive pain when compared with epidural fen-
tanyl and meperidine.1–5 It is very
parturients to enhance uterine contraction. Estimated
fluid deficits and maintenance requirements were
replaced with lactated Ringer’s solution intravenously.
Intermittent iv boluses of ephedrine 8 to 10 mg were
given, if necessary, for maintaining a stable blood pres-
sure. Midazolam, 2.5 mg iv, was given, if necessary, to
relieve the mental distress of mothers after delivery of
the baby; no supplementary analgesia was given.
At the end of surgery, parturients were randomly
assigned to four groups of 45 parturients to receive
dexamethasone, at doses of 10 mg, 5 mg or 2.5 mg,
or saline iv. The drug for injection was prepared as a
2 ml clear solution in identical syringes. One minute
after injection, all parturients received 3 mg preserva-
tive-free morphine in 10 ml isotonic sodium chloride
solution through the epidural catheter for postopera-
tive analgesia. The randomization process and the
identity of the study drugs were blinded from the par-
turients, the anesthesiologists during surgery, and the
investigators who collected the postoperative data.
Postoperatively, parturients were observed for 24
hr. A team of trained nurse anesthetists without
knowledge of which drugs the parturients had
received collected the postoperative data. During the
observation period, arterial blood pressure, heart rate,
and respiratory rate were monitored every four hours
except when parturients were sleep.
Nausea and vomiting was evaluated by the following
parameters: the incidences of nausea and vomiting,
episodes of vomiting, rescue antiemetics and successful
prevention. For the purpose of data collection, retching
(same as vomiting but without expulsion of gastric con-
tent) was considered as vomiting. A vomiting episode
was defined by events of vomiting that occurred in a
rapid sequence (<1 min between events). If the vomit-
ing were separated by more than one minute, they were
considered to be separate episodes. Vomiting which
occurred more than four times within 24 hr was con-
sidered as severe vomiting. Rescue antiemetics (4 mg
ondansetron iv) were given if vomiting occurred, or at
the parturients’ request. The treatment was repeated if
necessary. No vomiting and no antiemetic medication
during the 24-hr postoperative period was defined as
successful prevention. This was also the primary effica-
cy end point of the study. The data of nausea and vom-
iting were collected every four hours, except when
parturients were sleep, by direct questioning by a team
of specially trained nurse anesthetists or by spontaneous
complaint of the parturients.
E
convenient for clinical use and is widely accepted for
postoperative analgesia, e.g., post-Cesarean analge-
sia.1,4,5 However, despite its excellent analgesia prop-
erties, a high incidence of nausea and vomiting
(30-65%) has been reported.6–8 Among the antiemet-
ics currently used, serotonin subtype 3 (5-HT) antag-
3
onists (e.g., ondansetron, granisetron) possess good
efficacy, but high cost limits their widespread clinical
application.9,10 Other currently used antiemetics (e.g.,
anticholinergics, dopamine receptor antagonists, anti-
histamines) have side effects (e.g., restlessness, dry
mouth, changes in blood pressure, and extrapyramidal
symptoms).6,7,11,12
Dexamethasone is an effective antiemetic agent
with minimal side effects after single dose administra-
tion.13–18 It is effective in preventing chemotherapy-
related emesis and postoperative nausea and vomiting
(PONV).1 8 Recently, we also found that dexametha-
sone (8 mg) was effective in preventing nausea and
vomiting associated with epidural morphine for post-
Cesarean analgesia.1 4 Although effective, the mini-
mum effective dose of dexamethasone for this purpose
has not been determined. We, therefore, performed a
randomized and double-blinded study to evaluate
three doses of dexamethasone, compared with saline,
in preventing epidural morphine-related nausea and
vomiting in parturients undergoing Cesarean delivery.
Methods
The protocol was approved by the Hospital
Committee for Human Investigation and informed
consent was obtained from each parturient. One hun-
dred and eighty parturients, ASA physical status I or
II, 20-35 yr, scheduled for elective Cesarean delivery
under epidural anesthesia were enrolled in a random-
ized, double-blinded, and placebo-controlled study.
Parturients with a history of PONV, motion sickness
or gastrointestinal disorders were excluded. The par-
turients with body weight < 50 kg or > 90 kg were
also excluded. No premedication was given. Surgical
anesthesia to T4 was provided by 0.3 ml·kg– 1lidocaine
2% (with 1:100,000 epinephrine) followed by inter-
mittent small-dose injections of lidocaine 2% (with
epinephrine) as necessary through an epidural catheter
in the L3-4 or L4-5 interspace. Five hundred milliliters
lactated Ringer’s solution were given intravenously
before surgery to maintain a stable blood pressure.
After delivery of the baby, routine use of 10 units oxy-
tocin iv and 0.2 mg ergonovine im were given to all
Postoperative pain at the surgical wound was
assessed with a 10-cm visual analog scale (VAS; 0= no
pain to 10= most severe pain) score. When parturients
complained of pain and requested analgesia, 20 mg

Wang et al.: DEXAMETHASONE A N D EMESIS
187
TABLE I Patient’s demographics and operative characteristics
Dexamethasone
10 mg
Dexamethasone
5 mg
Dexamethasone
2.5 mg
Saline
Number (n)
Age (yr)
Weight (kg)
43
28
70
44
27
72
44
27
71
44
28
72
4
8
3
9
4
8
5
9
Height (cm)
Pariety (n)
157
2 (1-3)
54 18
70 22
360 (320-420)
0 (0-2.5)
10 (0-20)
1460 210
3
156
2 (1-3)
52 20
72 21
340 (300-420)
0 (0-2.5)
8 (0-24)
4
158
2 (1-3)
48 19
68 23
320 (300-400)
0 (0-2.5)
8 (0-20)
1360 180
7
4
157
3
2 (1-3)
54 21
74 22
360 (320-440)
0 (0-2.5)
10 (0-30)
1420 190
6
Duration of surgery (min)
Duration of anesthesia (min)
Total lidocaine administered (mg)
Total midazolam administered (mg)
Total ephedrine administered (mg)
Total iv fluid administered (ml)
Hospital stay (day)
1520 210
6
1
6
1
1
1
Values are numbers, mean SD, or median (range).
No significant differences among groups.
TABLE II Postoperative wound pain at rest (VAS scores) and proportion of patients requiring rescue analgesic
Time
(hr)
Dexamethasone
10 mg
Dexamethasone
5 mg
Dexamethasone
2.5 mg
Saline
4
8
20
24
2.1 0.9
1.8 0.9
2.2 1.4
2.1 1.3
11/43
2.2 1.0
1.9 1.1
2.3 1.2
2.1 1.2
10/44
2.1 0.9
2.1 0.9
2.4 1.6
2.2 1.5
11/44
2.2 1.1
2.2 1.2
2.6 1.5
2.4 1.4
14/44
Patients requiring rescue analgesic
Values are numbers or mean SD. VAS: visual analog scale;
No significant difference among groups.
TABLE III The evaluation of nausea and vomiting associated with epidural morphine for post-Cesarean analgesia
Dexamethasone
10 mg
Dexamethasone
5 mg
Dexamethasone
2.5 mg
Saline
Number (n)
Nausea/vomiting
Nausea
43
44
44
44
5 (12)
5 (11)
7 (16)
12 (27)
Vomiting
Total
3 (7)
8 (19)†
3 (7)
8 (18)†
7 (16)
11 (25)*
10 (23)
22 (50)
Vomiting episodes
0-4 times
>4 times
Rescue antiemetics
Successful prevention
2 (5)
2 (5)
1 (2)*
5 (11)*
39 (89)*
3 (7)
2 (5)
1 (2)*
4 (9)*
39 (91)*
1 (2)*
8 (18)
36 (82)
8 (18)
14 (32)
30 (68)
Values are number of patients (%).
Successful prevention was defined as no vomiting and no antiemetic medication during a 24 hr postperative period.
†P < 0.01; *P < 0.05 when compared with saline group using a 4 x 2P2 test followed by a 2 x 2P2 test or Fisher’s exact test, as appropriate.
No significant differences among Groups dexamethasone 10 mg and 5 mg.
tenoxicam iv (every 12 hr) was given. Pruritus was
assessed on a three-point ordinal scale (0= none, 1=
pruritus but only in a small area of the body, 2= gen-
eralized pruritus). Pruritus was treated with im
diphenhydramine (20 mg every four hours as needed).
The occurrence of side effects accompanying dex-
amethasone usage, such as wound infection or delayed
wound healing during their stay in hospital was evalu-

188
CANADIAN JOURNAL OF ANESTHESIA
ated and reported by an obstetrician (Dr. Liu). Any
other side effects were also recorded. Duration of hos-
pital stay was recorded too.
nificant. Dexamethasone 2.5 mg was only partially
effective.
The incidence of pruritus among groups was not
different and was in the range of 41 to 47% in the dex-
amethasone groups and 43% in the saline group. The
severity of pruritus among groups was not significant.
Nine to 15% of parturients in the dexamethasone
groups and 14% of parturients in the saline group
requested im diphenhydramine for the management
of pruritus. No other side effect associated with the
usage of dexamethasone was found.
Sample size was predetermined by using a power
analysis based on the assumptions that (a) the total
incidence of nausea and vomiting in the saline group
would be 50%,1 4 (b) a 40% reduction in the total inci-
dence of nausea and vomiting (from 50% to 30%) in
the treatment group would be of clinical relevance, and
(c) a =0.05, ß=0.2.19 The analysis showed that 40 par-
turients per group would be sufficient to detect the
antiemetic effect of small dose of dexamethasone (2.5
mg).19 A series of one-way analyses of variance were
conducted to examine differences among the four
groups with respect to parametric variables. If a signif-
icant difference was found, the Bonferroni t-test was
used to detect the intergroup differences. The Kruskal-
Wallis test was used to determine differences among
the four groups with respect to nonparametric vari-
ables, followed by the Mann-Whitney U test for inter-
group differences. Categorical variables were analyzed
by using a series of 4 × 2P2 tests to determine differ-
ences among the four groups, followed by 2 × 2P2 tests
or Fisher’s exact tests, as appropriate, for intergroup
differences. All follow-up analyses were corrected for
the number of simultaneous contrasts using the
Bonferroni adjustments. A P value < 0.05 was consid-
ered statistically significant.
Discussion
Many reports have suggested the use of 8 to 10 mg
dexamethasone as a prophylactic antiemetic agent for
PONV.13–18 The antiemetic effect of 8 to 10 mg dex-
amethasone is equal to that of 4 mg ondansetron10,18
and 1.25 mg droperidol.1 3 Recently, we have also
shown that 8 mg dexamethasone reduced the inci-
dence of nausea and vomiting related to epidural mor-
phine in the treatment of post-Cesarean pain.1 4
However, the minimum effective dose of dexametha-
sone for this purpose was not determined. In the cur-
rent study, We found that 10 mg and 5 mg
dexamethasone were more effective than saline in pre-
venting nausea and vomiting associated with epidural
morphine for post-Cesarean analgesia. The differences
between 10 mg and 5 mg dexamethasone were not
statistically significant. Dexamethasone 2.5 mg was
partially effective. Dexamethasone 5 mg iv may be the
minimum effective dose for this purpose.
We also found that dexamethasone did not influ-
ence the efficacy of epidural morphine-related analge-
sia. Parturients receiving 2.5 mg, 5 mg or 10 mg
dexamethasone requested similar amounts of rescue
analgesic and reported similar intensities of postoper-
ative pain. Besides, dexamethasone did not influence
the occurrence of pruritus related to epidural mor-
phine for post-Cesarean analgesia.
The exact mechanism by which epidural morphine
exerts an emetic action is alleged to be activation of opi-
oid receptors in the chemoreceptor trigger zone of the
fourth ventricle caused by cephalad migration of the
morphine.8 However, the exact mechanism by which
dexamethasone, a glucocorticoid, exerts an antiemetic
action after epidural morphine is not known.1 8
Glucocorticoids have been shown to have various
effects on the central nervous system; they regulate
transmitter levels, receptor densities, signal transduc-
tion, and neuronal configuration.20,21 In the nucleus of
the solitary tract, the nucleus of raphe, and the area
postrema, numerous glucocoriticoid receptors are
found.21,22 These nuclei are well known to have consid-
Results
Of the 180 parturients enrolled in the study, five were
withdrawn due to incomplete data collection.
Therefore, 175 parturients completed the trial. There
were no differences among groups with respect to age,
weight, height, parity, duration of surgery and anes-
thesia, the consumptions of lidocaine, midazolam,
ephedrine and iv fluid during surgery, and duration of
hospital stay (Table I).
After surgery, all parturients received epidural 3 mg
morphine for pain relief. All parturients reported low
VAS pain scores and the differences among groups
were not significant. In addition, the proportions of
parturients requiring rescue analgesic among groups
were not significantly different, neither (Table II).
Parturients who received dexamethasone, either 10
mg or 5 mg, were different from those who received
saline alone in the following parameters: the total
incidences of nausea and vomiting, incidence of > 4
vomiting episodes, the number of parturients requir-
ing rescue antiemetics, and the the total number of
parturients with no vomiting and/or no antiemetic
medication (Table III). The differences between dex-
amethasone 10 mg and 5 mg were not statistically sig-

Wang et al.: DEXAMETHASONE A N D EMESIS
189
blind, dose-response comparison of epidural fentanyl
versus sufentanil analgesia after Cesarean section.
Anesth Analg 1997; 85: 365–71.
erable neuronal activities on the regulation of nauseat-
ing and vomiting responses.8,23 Dexamethasone may
exert its antiemetic action through these nuclei.
Some factors which may interfere with the inter-
pretation of the study result, such as consumptions of
ephedrine, midazolam, diphenhydramine and iv fluid,
were also evaluated in our study.23,24 We found that
the intraoperative consumptions of ephedrine, mida-
zolam and iv fluid were similar among groups. In
addition, the use of diphenhydramine among groups
for the treatment of pruritus was also similar.
Therefore, differences in the occurrence of nausea and
vomiting among the groups can be attributed to the
study drugs.
In a previous study, we found that iv dexametha-
sone has a delayed onset of action for both nausea and
vomiting.2 5 The lag time was about two hours.25 In
patients receiving epidural morphine, the occurrence
of nausea and vomiting is usually two to four hours
after medication.1, 8 In our study, iv dexamethasone
was given one minute before the administration of
epidural morphine. Under this design, dexamethasone
was considered to be an active antiemetic if the dosage
was appropriate.
Multiple-dose corticosteroid therapy (>1 week)
may cause side effects, such as increased risk of infec-
tion, glucose intolerance, delayed wound healing,
superficial ulceration of gastric mucosa, avascular
necrosis of femoral head, and adrenal supression.20,26
However, these side effects are not found after a sin-
gle dose of dexamethasone therapy.13–18 In the current
study, a single dose of 2.5 to 10 mg dexamethasone
did not cause wound infection or delay wound heal-
ing. In addition, no other side effects were also found
after the usage of a single dose of dexamethasone.
In conclusion, 10 mg and 5 mg dexamethasone
were more effective than saline in preventing epidural
morphine-related nausea and vomiting in parturients
undergoing Cesarean delivery. The difference
between dexamethasone 10 mg and 5 mg was not sig-
nificant. Dexamethasone 2.5 mg was partial effective.
We suggest that dexamethasone 5 mg iv is the mini-
mum effective dose for this purpose.
4 Fuller JG, McMorland GH, Douglas MJ, Palmer L.
Epidural morphine for analgesia after Caesarean sec-
tion: a report of 4880 patients. Can J Anaesth 1990;
37: 636–40.
5 Harrison DM, Sinatra R, Morgese L, Chung JH.
Epidural narcotic and patient-controlled analgesia for
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6 Sanansilp V, Areewatana S, Tonsukchai N. Droperidol
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8 Chaney MA. Side effects of intrathecal and epidural
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9 Fujii Y, Tanaka H, Toyooka H. Granisetron-dexametha-
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13 Wang J-J, Ho S-T, Lee S-C, Liu Y-C, Liu Y-H, Liao Y-
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