Acta Anaesthesiologica Taiwanica 50 (2012) 150e152

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Acta Anaesthesiologica Taiwanica

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Original Article

A placebo-controlled, double-blind, randomized study of single-dose

intravenous diclofenac for pain relief after a cesarean section
Somboon Thienthong 1 *, Chompilas Chongsomchai 2, Walairat Kemthong 2
1
Department of Anesthesiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
2
Department of Obstetrics and Gynecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

a r t i c l e i n f o a b s t r a c t

Article history: Background: This study was conducted to avoid the pain of an intramuscular injection of diclofenac after
Received 25 June 2011 a cesarean section, by modifying it to an intravenous infusion by diluting it with 5% dextrose in 100 mL of
Received in revised form water.
30 June 2012
Objective: The aim of this study was to determine the efficacy of a single-dose modified diclofenac being
Accepted 4 December 2012
given intravenously, instead of intramuscularly, for pain relief after a cesarean section.
Study design: A double-blind, randomized controlled trial was conducted.
Key words:
Participants: We enrolled 30 patients who underwent cesarean sections with Pfannenstiel skin incision.
cesarean section;
diclofenac;
Methods: All patients received 2.2e2.5 mL of 0.5% bupivacaine with 0.2 mg morphine for spinal anes-
injections, intravenous; thesia. The participants were equally and randomly allocated to two groups to receive intravenous
pain, postoperative diclofenac or placebo at 12 hours postoperatively. Both groups received the same regimen for post-
operative pain control.
Main outcome measurements: The severity of postoperative pain was measured directly using a verbal
numerical rating scale (0e10) and a pain-relief scale (1e4), and indirectly from the amount of tramadol
used.
Results: The characteristics of the two groups of patients were similar. The mean postoperative pain relief
at 24 hours in the study group was better than that in the control group (3.14
0.66 vs. 2.13
0.99;
p < 0.05). The severity of postoperative pain at 24 hours and the amount of tramadol used were not
different between groups.
Conclusion: Intramuscular diclofenac (75 mg), modified by diluting it with 5% dextrose in 100 mL of
water, for intravenous administration in combination with spinal morphine (0.2 mg) provided good
analgesia after a cesarean section within 24 hours when assessed by the pain-relief scale; however, the
mean pain intensity was not different.
Copyright Ó 2012, Taiwan Society of Anesthesiologists. Published by Elsevier Taiwan LLC. All rights
reserved.

1. Introduction Nonsteroidal anti-inflammatory drugs (NSAIDs), when

combined with opioids, can help reduce opioid consumption and
Pain during and after a cesarean section is the greatest concern improve the quality of pain control.4,5 Diclofenac is an NSAID
expressed by patients.1 Indeed, inadequate pain control after widely used in various forms or preparations (e.g., intramuscular,
a cesarean section can significantly detract from the sense of well- intravenous, oral, and suppository preparation) for pain control. In
being and joy of the mother in the immediate postpartum period, our institute, only the intramuscular and oral forms are available;
by affecting maternal activities such as the pleasure of breast- an oral diclofenac is not allowed during the nothing per oral or NPO
feeding.2 In our previous study, we found that the proportion of period after a cesarean section. Since pain prevalence after the
patients who experienced moderate to severe pain during the 24- cesarean section in our institute remains high, we are trying to
hour postcesarean section period was high.3 improve the status quo by including the use of diclofenac during
this transition period. However, to avoid the painful intramuscular
injection of diclofenac, the intramuscular preparation was modified
for intravenous infusion by diluting it with 5% dextrose in 100 mL of
* Corresponding author. Department of Anesthesiology, Faculty of Medicine,
Khon Kaen University, Khon Kaen 40002, Thailand. water. A single dose of diclofenac was designed for this study
E-mail address: somthi@kku.ac.th (S. Thienthong). because the authors wanted to make sure that the modified

1875-4597/$ e see front matter Copyright Ó 2012, Taiwan Society of Anesthesiologists. Published by Elsevier Taiwan LLC. All rights reserved.
http://dx.doi.org/10.1016/j.aat.2012.12.005
Intravenous diclofenac for pain relief 151

technique worked well prior to incorporating it into practical use. Pregnant women underwent cesarean delivery
Therefore, the purpose of this study was to determine the efficacy under spinal anesthesia plus morphine (n = 30)
of such a modified, single-dose diclofenac given intravenously
instead of intramuscularly for pain relief after a cesarean section.
Randomized

2. Materials and methods

Pain assessment at 12 h post operation
The study was approved by the Khon Kaen University Ethics
Committee. Enrolled in the study were 30 pregnant women who
were to undergo lower segment cesarean section with Pfannenstiel Control group (n = 15) Study group (n = 15)
skin incision under spinal anesthesia in July 2008. Written 5% D/W 100 mL IV drip Diclofenac 75 mg+ 5% D/W
informed consent was obtained from each woman. Exclusion in 10 min + standard 100 mL IV drip in 10 min +
pain control standard pain control
criteria for participation included patients in whom the use of
NSAIDs was contraindicated, with a history of NSAIDs allergy and
a midline skin incision or the surgery under general anesthesia.
Spinal anesthesia was performed by an anesthesiologist in the Outcomes measured at 24 h post operation
operating room with 2.2e2.5 mL of 0.5% bupivacaine plus 0.2 mg of 1. Severity of pain
morphine. All patients received standard care during the operation 2. Amount of analgesic use
3. Pain relief
and in the recovery room, after which they were transferred to the
4. Side effects
postpartum ward. At the postpartum ward, 12 hours after the
caesarean section, patients were randomly allocated (by computer
randomization) to receive 75 mg diclofenac sodium diluted with 5% Data analysis
Study group (n = 14)*
dextrose in 100 mL of water or placebo, in accordance with the order
Control group (n =
sealed in an envelope, coded by the investigator. The reason for
starting the study medication at 12 hours after spinal anesthesia was
Fig. 1. Patient flow diagram. * One patient in the diclofenac group was dropped from
to make sure that analgesic effect of bupivacaine had faded. Prior to the study because she had internal bleeding and needed re-exploration.
starting the study medication, pain scores were recorded (to be the
baseline data) using a verbal numerical rating scale (VNRS, a scale of
0e10: 0 ¼ no pain and 10 ¼ very severe pain). The trained ward under general anesthesia was excluded from the study. The re-
nurses, who recorded pain scores at the postpartum ward, were exploration was necessary due to a surgical problem caused by
ignorant of the study regimen, and the study solutions were prepared slippage of bilateral tubal resection stumps. The baseline charac-
by the anesthesiologist who performed the spinal analgesia. teristics of participants and operative factors were similar for both
The study solution was then administered over a period of 10 the groups, except that the operative time and gravida were longer
minutes. Later, at 24 hours post operation, the patients were again (Table 1) and the pain score at rest appeared to be lower (Table 2)
evaluated for the severity of their pain and pain relief by a four- for the diclofenac group.
point pain-relief scale (1 ¼ no pain relief, 2 ¼ poor pain relief, The mean pain score 24 hours after surgery was not statistically
3 ¼ good pain relief, and 4 ¼ excellent pain relief) (Fig. 1). different between two groups, nor was the amount of tramadol
Postoperative fever (>37.5  C), nausea and vomiting (which used (Table 2). Pain relief after receiving diclofenac (measured at 24
needed treatment), abdominal discomfort (reported by patient as hours postoperatively) was significantly different between the two
“yes” or “no”), and length of stays were also assessed. All the groups (3.14
0.66 vs. 2.13
0.99; p ¼ 0.003). There was no
patients received the same regimen for postoperative pain control statistically significant difference between groups vis-à-vis post-
(in addition to the 0.2 mg single doses of spinal morphine), namely operative fever, nausea, vomiting, abdominal discomfort, or length
50 mg intravenous tramadol every 6 hours as requested. The of hospital stay.
patients then had their pain scores reassessed within 15 minutes. If
pain persisted (i.e., pain scores 5) a 25-mg intravenous rescue 4. Discussion
dose of tramadol was given.
The sample size was calculated based on a power analysis, using The current study demonstrated that when a diclofenac intra-
the mean pain score at rest (1.9
1.1) from the previous study muscular formula is modified to an intravenous infusion (by
investigating the effectiveness of a single dose of 75 mg diclofenac
for pain relief at 24 hours after a cesarean section.6 With a power of
80% for the detection of 50% difference, a ¼ 0.05, and b ¼ 0.2, we Table 1
Baseline characteristics and operative factors.
needed at least 14 participants in each group. We had 15 partici-
pants in each group. Characteristics Diclofenac group Placebo group p
(n ¼ 14) (n ¼ 15)
The continuous data were presented as means
standard
deviation (SD). The Student t test was used to compare the Age (y
SD) 32.50
4.78 30.60
4.40 0.20
Maternal weight 67.88
10.40 66.96
12.20 0.80
continuous variables. Pain-relief scores were present as mean
SD (kg
SD)
and analyzed by unpaired t test. Other categorical data (such as Gestational age 37.21
1.98 37.87
0.91 0.11
abdominal discomfort) were presented as frequency, while the Chi- (wk
SD)
square test was used to compare these variables where appropriate. Gravidity 2.06 þ 0.96 1.33
0.49 0.02
Operative time 71.79
20.90 57.13
13.73 0.02
A p value of <0.05 was considered statistically significant.
(min
SD)
Tubal resection (%) 6/14 (42.85) 4/15 (26.67) 0.25
3. Results Surgeon
Resident (%) 7/14 (50.00) 8/15 (53.33) 0.99
The total number of patients in the study groups was 14 because Faculty (%) 7/14 (50.00) 7/15 (46.67) 0.06

one patient who had internal bleeding and needed re-exploration SD ¼ standard deviation.
152 S. Thienthong et al.

Table 2 there is a low risk of any hazard to breastfed infants.8,9 Moreover,

Outcome measurements. the American Academy of Pediatrics states that diclofenac is
Outcome measurement Diclofenac group Placebo group p considered compatible with breastfeeding.
(n ¼ 14) (n ¼ 15) Normally, diclofenac is recommended to be administered three
Baseline VNRS at 12 h post operation (mean
SD) times daily or once every 8 hours, but when combined with
At rest 1.57
1.91 3.07
0.25 0.09 morphine its analgesic effect lasts longer. The limitation of the
While ambulating 4.36
2.49 5.60
2.29 0.17
present study is that we did not evaluate the severity of pain at
VNRS at 24 h post operation (mean
SD)
At rest 2.50
2.06 3.73
2.63 0.17 more than one point (i.e., at 3, 6, and 12 hours after being given the
While ambulating 5.57
2.17 5.80
2.36 0.78 study drug), so we do not know the progression of pain relief.
Pain relief (mean
SD) 3.14
0.66 2.31
0.99 0.003 Multiple points (or at least one more point at 6 hours) would have
Amount of tramadol used 16.07
27.04 35.00
32.45 0.10 provided valuable information. In addition, the small sample size is
(mg
SD)
Postoperative fever 0 0 d
another limitation of this study.
Abdominal discomfort 0 0 d
Nausea/vomiting 0 0 d
Length of stay 3.07
0.26 3.07
0.26 0.96
5. Conclusion

SD ¼ standard deviation; VNRS ¼ Verbal Numerical Rating Scale.

Intramuscular diclofenac 75 mg (modified by diluting it in 5%
dextrose in 100 mL of water) for intravenous route delivery, in
diluting it with 5% dextrose in 100 mL of water), it is effective for combination with spinal morphine 0.2 mg, provided good analgesia
pain relief after a cesarean section, as rated by patients using 1e4 within 24 hours after a cesarean section when assessed by the pain-
scales (3.14
0.66 vs. 2.13
0.99; p ¼ 0.003), although pain relief scale; however, the mean pain intensity was not different.
intensity (measured by numerical rating scale) and tramadol used
during the 12 hours after administration were not different. There Acknowledgments
were some uncontrolled factors in the baseline data, which were
different between groups that had confounded pain relief, for The authors wish to thank the nurses of obstetrics and gyne-
example the number of gravidity as we know repeated incisions cology wards for data collection, residents and nurses of the
could be less painful, tubal resection, operation time, and pain anesthesiology department for preparing study solution, and Mr
intensity prior to the administration of study solution. The amount Bryan Roderick Hamman and Mrs Janice Loewen-Hamman for their
of tramadol used in 24 hours seemed to be higher in the placebo assistance in the presentation of the manuscript in English.
group, but data were not clear enough to demonstrate whether its
use was higher in the first 12 hours. All these confounding factors
made pain intensity inconsistent with pain relief. References
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