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doi:10.1111/jog.12465 J. Obstet. Gynaecol. Res. Vol. 40, No. 11: 2152–2157, November 2014

Intravenous infusion of paracetamol for

intrapartum analgesia

Karim H. I. Abd-El-Maeboud, Ahmed E. H. Elbohoty, Walid E. Mohammed,

Hatem M. Elgamel and Walid A. H. Ali
Department of Obstetrics and Gynecology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Abstract
Aim: To evaluate the efficacy and adverse effects of an i.v. infusion of paracetamol during the active phase of
labor as compared with sterile water (placebo) as a method for intrapartum analgesia.
Methods: In a triple-blind, randomized, placebo-controlled trial, 120 low-risk primiparous women presenting
in active labor at Ain Shams University Maternity Hospital, Cairo, Egypt, between August 2011 and October
2012, were allocated to receive either 1000 mg i.v. of paracetamol (n = 60) or sterile water (n = 60). The primary
outcomes were the efficacy of the drug to supply adequate analgesia as measured by a change in the visual
analog scale (VAS) pain intensity score at various time points after drug administration and the need for
additional rescue analgesia. The secondary outcomes included the presence of adverse maternal or fetal events.
Results: Compared to controls, i.v. infusion of paracetamol was associated with significantly lower VAS score
15 and 30 min after the start of medication; also, there was a significantly lower incidence of need for rescue
medication (8/57 [14%] vs 49/59 [83.1%], P < 0.001) at 60 min after the start of medication. There were no
recorded maternal adverse effects in either group. There were no differences in occurrence of intrapartum fetal
distress or neonatal Apgar scores between both groups.
Conclusion: Paracetamol appears to be a safe and effective medicine that can be used during the intrapartum
period.
Key words: analgesia, intrapartum, paracetamol, sterile water.

Introduction in need of effective analgesia;5 however, it prolongs the

Childbirth is an important experience in a woman’s
life;1 nevertheless, labor pains are considered to be one
of the most intense and stressful experiences,2 being
compared in intensity to severe cancer pain or pain
from the amputation of a digit.2,3 Adequate analgesia
during labor has a positive influence on the course of
labor,3 and most women who deliver in modern obstet-
ric units request some form of pharmacological or non-
pharmacological pain relief.4 Epidural analgesia using
opioids is the most potent method for women in labor
duration of the second stage of labor by 15–30 min and
may increase the rate of instrument-assisted vaginal
deliveries as well as that of oxytocin administration.6,7
i.m. administration of narcotics can also reduce the
pain of labor pain but this method is limited by
negative side-effects such as maternal drowsiness,
nausea and vomiting as well as neonatal respiratory
depression.8
Paracetamol has been widely used for over a century
as an effective analgesic and as an antipyretic agent.9 Its
efficacy and tolerability are well established and, in

Received: September 2 2013.

Accepted: April 2 2014.
Reprint request to: Dr Ahmed Elsayed Hassan Elbohoty, Department of Obstetrics and Gynecology, Faculty of Medicine, Ain Shams
University, 8 TassemElawkaf, Elswah Square, Cairo 11566, Egypt. Email: elbohoty79@yahoo.com
ClinicalTrials.gov identifier: NCT01428375.

2152 © 2014 The Authors

Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology

contrast with other analgesics, it has a favorable safety
profile.10 It can be administrated p.o. or rectally.11 At
therapeutic doses, it is associated with fewer adverse
effects than either opioids or non-steroidal anti-
inflammatory drugs.12 It is metabolized through conju-
gation with glucoronic acid and sulfate to be excreted
into the urine. A small fraction (<4%) is metabolized by
cytochrome P450 to a reactive intermediate (N-acetyl
benzoquinone imine) which is toxic for the hepatocytes
and, under normal conditions of use, is rapidly detoxi-
fied by reduced glutathione and eliminated in the
urine after conjugation with cystein.13 The action of
paracetamol at a molecular level is unclear but could be
central, which explains the different effect from non-
steroidal anti-inflammatory drugs on uterine contrac-
tions and premature closure of the ductus arteriosus.14
Although paracetamol has been widely used as an
effective and safe analgesic medication,9,10 there is a
paucity of studies assessing its intrapartum use. It has
been shown that the metabolism of paracetamol is
unchanged in pregnant woman,15 and increasing
towards term in the fetus,16–18 with absent reports of
fetal insult when used in the standard dose in healthy
women at term.19 Considering this, it is plausible to
assume its safety in use as an intrapartum analgesia.
Hence, a pilot single-arm trial in Ain Shams University
Hospital, Cairo, Egypt, which recruited 35 laboring
women in the first stage of labor who received a single
i.v. dose of 1000 mg paracetamol showed no adverse
effects in the mothers or the neonates (A. E. H. E.,
unpubl. data). Another study was also done in Ain
Shams University Hospital comparing i.v. infusion of
paracetamol versus i.v. pethidine as an intrapartum
analgesic in the first stage of labor which showed
a comparable effect between both medicines, but
paracetamol had fewer adverse effects and shorter
duration of labor.20 However, in the previous study, it
was not possible to be double-blinded and the effect of
paracetamol on labor duration might have been
affected by the comparison to pethidine. So, it was
plausible to compare paracetamol with placebo.
The aim of the present study was to evaluate the
efficacy and adverse effects of an i.v. infusion of
1000 mg paracetamol during the active phase of labor
as compared with sterile water (placebo) as a method
for intrapartum analgesia.
Methods
The present single-center, triple-blind, randomized,
placebo-controlled trial recruited women in labor pre-
© 2014 The Authors
Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Paracetamol for intrapartum analgesia
senting for delivery at Ain Shams University Maternity
Hospital, Cairo, Egypt, between August 2011 and
October 2012. The participating women, primary inves-
tigator and statistician were all blinded (triple-blind
design) to group assignment until after analysis had
been performed by the statistician. Following data
analysis, the manufacturing company was asked to
notify us with this assignment. The protocol of the
study was approved by the Research and Ethics Com-
mittee, Department of Obstetrics and Gynecology,
Faculty of Medicine, Ain Shams University. All women
fulfilling the recruitment criteria received an informa-
tive discussion about the nature of the study. Those
agreeing to enter the study signed a written informed
consent.
Women presenting in active labor and requesting
analgesia in the first stage of labor were screened for
study eligibility. Throughout the study period, a
maximum of three parturients were recruited weekly
on Thursdays. The inclusion criteria were primi-
gravidity, low-risk pregnancy, age of 18–35 years, spon-
taneous onset of labor at term (37–42 weeks’ gestation)
with cervical dilatation of 3–4 cm, and a single live
fetus in cephalic presentation. The exclusion criteria
included clinical evidence of cephalopelvic dispropor-
tion, any medical disorder during pregnancy, induc-
tion of labor, use of any other kind of analgesia before
recruitment to the study, scarred uterus, fetal dis-
tress and previous history of hypersensitivity to
paracetamol. Demographic data, including age and
gestational age, were recorded.
The sample size was calculated using EpiInfo version
6.0, setting the power (β) at 80% and the significance
level (α) at 0.05. Data from a pilot study (A. E. H. E.,
unpubl. data), indicated that the mean difference in
visual analog scale (VAS) after 1 h of administration of
i.v. infusion paracetamol was 0.21 ± 0.19 (95% confi-
dence interval [CI], 0.14–0.28). Calculation according to
these values produced a minimal sample size of 50
cases in each group to find such a difference at a similar
or narrower CI. Assuming a dropout rate of 20% (e.g.
use of rescue analgesic, or shift to cesarean section as a
result of any intervening problem), the total sample
size was 120 cases, randomized into two equal
groups.
After enrollment, each participant was allocated the
next available number in a concealed sequence of a
computer-generated randomization plan, which deter-
mined the drug to be used. The participants were
randomly allocated to one of two groups: in the
paracetamol group (n = 60), women received a 100-mL
2153
K. H. I. Abd-El-Maeboud et al.
i.v. infusion containing 1000 mg of paracetamol over
15 min; and in the placebo group (n = 60), women
received an i.v. infusion of 100 mL of sterile water for
injection over 10 min. The bottles of both medicaments
were the same shape and every bottle had a number
which was assigned by a randomization computer
program. The parturient women, clinical investigators
and statistician were all blinded regarding grouping
till after final data analysis.
Labor was followed up according to the hospital’s
protocols with artificial rupture of membranes and
subsequent application of an oxytocin infusion if there
were fewer than three contractions in 10 min, each
lasting less than 40 s. Participants reported pain inten-
sity on a 100-mm VAS, bounded by ‘no pain’ (at zero
point) and ‘the worst pain’ (at 100 mm point). Pain
assessment was performed by one person (W. A. H. A.)
having no role in patient enrollment, to minimize sub-
jectivity in pain score assessment. Participants who had
not delivered within 4 h and still needed analgesia
were given a further infusion of the same treatment;
the minimum interval between each administration
was 4 h. Those who had requested another or rescue
analgesic after the elapse of 60 min were excluded from
follow-up of pain assessment.
Spontaneously observed and reported adverse
events, both maternal (dizziness, tachycardia, dyspnea,
vomiting, blurred vision, dryness of the mouth, and
significant changes in blood pressure [≥30 mmHg
systolic or ≥15 mmHg diastolic], and fetal or neonatal
non-reassuring cardiotocography including fetal
tachycardia, low Apgar scores at 1 and 5 min, and need
for admission to the intensive care unit) were recorded.
The duration of labor was also calculated and recorded.
The primary outcome measures were the efficacy
of the drug to supply adequate analgesia as indicated
by change in the VAS pain intensity score at 15 min,
30 min from drug administration and dropout rate
resulting from the need for rescue or additional
analgesia. Secondary outcome measures included the
presence of maternal or fetal adverse events during the
study.
Data are presented as descriptive statistics (range,
mean and standard deviation for metric data; and
range and median for discrete data). Both groups were
compared using Student’s t-test or two-way anova (for
quantitative parameters), and χ2-test or Fisher’s exact
test exact test (for categorical parameters). Excel 2007
(Microsoft, Redmond, WA, USA) and SPSS version 16.0
(IBM, Armonk, NY, USA) were used for data presenta-
tion and statistical analysis.
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Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Results
Among 136 women interviewed, 120 were enrolled in
the study and only 116 completed the study as four
women withdrew from the study after recruitment
(Fig. 1). All of the participants in the two groups were
primigravida in the active stage of labor with com-
parable age, gestational age and cervical dilatation
(Table 1).
There was no statistical difference in pain scores
between the two groups initially (Table 2). The
high pain score in the included women in this study,
which may not be observed in all laboring women at
this stage of labor, may be explained by recruiting
only those deemed in need of analgesia. The pain
scores after 15 and 30 min from receiving the
drugs were significantly higher in those receiving
sterile water (Table 2). From 1 to 4 h, the rates
of discontinuation of medication due to receiving
rescue analgesia were stable, being eight of 57
patients (14%) versus 49 of 59 (83.1%) in the
paracetamol and control groups, respectively
(P < 0.001). On the other hand, by the elapse of 4 h,
the overall rate of discontinuation of medication
due to delivery was nine of 57 and four of 59 in
the paracetamol and control groups, respectively.
However, the VAS pain scores after 1 h were compa-
rable in both groups (19.76 vs 19.88) as most of
women in the sterile water group received additional
analgesia, and hence they were excluded from analy-
sis. The exclusion of subjects who received rescue
analgesic from VAS score after 1 h does not represent
a bias in intention to treat analysis as effectiveness of
paracetamol was already proved by lower VAS scores
achieved. Furthermore, incorporation of these subjects
in VAS score assessment after 60 min would have
been a comparison between paracetamol and other
analgesics being received by subject rather than
placebo. The treatments were repeated in each group
after 4 h as it was planned in the study, but the
remaining number of women in both groups were
much lower as more than 50% of participants had
already delivered, which made the comparison
non-plausible.
There was no difference in the percentage of vaginal
deliveries or the mean drug to delivery interval
between both groups. No maternal adverse effects
were recorded in any group. There were no differences
in the occurrence of intrapartum fetal distress or
lowered neonatal Apgar scores between both groups
(Table 3).
© 2014 The Authors
 Paracetamol for intrapartum analgesia

Enrollment Assessed for eligibility (n=136)

Excluded (n=16 )
♦ Not meeting inclusion criteria (n=16)
♦ Declined to participate (n=0)
♦ Other reasons (n=0)

Randomized (n=120)

Allocation

Allocated to intervention (n=60) Allocated to intervention (n=60)

♦ Received allocated intervention (n=60) ♦ Received allocated intervention (n=60)
♦ Did not receive allocated intervention (give ♦ Did not receive allocated intervention (give
reasons) (n= 0 ) reasons) (n= 0 )

Follow-Up

Lost to follow-up (give reasons) (n=0) Lost to follow-up (give reasons) (n=0)

Discontinued intervention (n=1) Discontinued intervention (n=3)

Analysis

Analysed (n=59) Analysed (n=57)

♦ Excluded from analysis (give reasons) (n=0) ♦ Excluded from analysis (give reasons) (n=0)

Figure 1 Flow diagram of study participants.

Table 1 Demographic and clinical data†

Sterile water Paracetamol t P*
group (n = 59) group (n = 57)
Age (years) 22.5 ± 3.3 22.6 ± 3.7 0.269 0.788
Gestational age (weeks) 38.9 ± 1.1 39.2 ± 1.3 1.532 0.128
Cervical dilatation at drug administration (cm) 3.5 ± 0.5 3.3 ± 0.5 1.588 0.115
*Student’s t-test. †Values are given as mean ± standard deviation.

Discussion gesia is superior to placebo as 83.1% (49/59) of women

receiving placebo requested rescue analgesia while
The findings of the present study demonstrate that the only 14% (8/57) of women received paracetamol after
use of i.v. paracetamol injection for intrapartum anal- elapse of 4 h. It was also obvious that pain scores after

© 2014 The Authors 2155

Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
K. H. I. Abd-El-Maeboud et al.

Table 2 Pain assessment by visual analog scale score after administration of

paracetamol or placebo†
Time Sterile water group Paracetamol group P*
(n = 59) (n = 57)
At drug administration 90.37 (89.04–91.85) 88.77 (85.17–91.85) 0.308
After 15 min 77.58 (71.65–85.50) 28.84 (22.91–40.24) 0.000
After 30 min 82.19 (72.26–86.54) 26.33 (20.67–36.6) 0.000
*Two-way anova test. †Values are given as mean and 95% confidence interval.

Table 3 Comparison of intrapartum and postpartum events†

Sterile water Paracetamol P
group (n = 59) group (n = 57)
Cesarean delivery 9 (15.3%) 11 (19.3%) 0.564
Interval between drug and vaginal delivery (h) 6.6 ± 4.6 7.1 ± 3.6 0.558
Fetal adverse effects 5 (8.5%) 4 (7.1%) 0.790
Apgar score
At 1 min 7 (5–8) 7 (1–9) 0.827
At 5 min 9 (8–9) 9 (6–9) 0.786
†Values are given as number (percentage), mean ± standard deviation or median (range).

15 and 30 min from receiving the placebo were signifi-
cantly higher in those who received the placebo com-
pared to those who received paracetamol. Thereafter,
and up to 4 h after drug administration, the pain scores
were comparable, indicating good analgesic effect in
the paracetamol group compared to the placebo group
where additional analgesic was supplied. This suggests
that the duration of analgesia with paracetamol lasts for
up to 4 h compared to less than 3 h in a previous
study.20
Regarding VAS score analysis, although the initial
numbers of women in both groups were comparable
(59 received placebo while 57 received paracetamol), it
dropped after 1 h, being much lowered in the placebo
group (9 vs, 48; respectively), as all the women who
received rescue analgesia were excluded from the
analysis at this point (Table 2). This discrepancy was
not clear in the previous study as there was no signi-
ficant difference in the need of rescue analgesia
between women who either received pethidine (20%)
or paracetamol (13.5%).20 Another observed difference
in the present study was that the mean VAS after the
initial one was always lower than corresponding values
in the previous study20 which could be due to the dif-
ference in the observer and intrapartum quality of care,
and this effect lasted for 4 h which gave us reassuring
data about the duration of effectiveness of paracetamol.
There was no difference in the mean drug to delivery
interval between both groups although there was a pro-
posed shortening effect in the last trial compared to the
pethidine.20 This noticed effect might have been due to
the prolonging effect of pethidine which was also
found in a previous study with hyoscine.21
Many of the pharmacologic methods for intrapar-
tum analgesia have drawbacks, especially opioid-
derived medicines like pethidine which can lead to
maternal adverse effects including sedation, respira-
tory depression, delayed gastric emptying, nausea and
vomiting, and neonatal adverse effects including respi-
ratory depression and decreased Apgar scores.12,22 It is
universally agreed that epidural analgesia is the most
effective method of pain relief during labor and child-
birth, however, risks and costs of intrapartum epidural
analgesia are barriers to its liberal use.23–25 Studies
of laboring women have suggested an association
between the use of conventional lumbar epidural anal-
gesia for pain relief during labor and longer first and
second stages of labor, an increased incidence of fetal
malposition, an increased use of oxytocin and instru-
mental delivery, hypotension, inadvertent dural punc-
ture and headache.26–30 Our data show no maternal
adverse effects in either study group. There were also
no differences in occurrence of intrapartum fetal dis-
tress or neonatal Apgar scores between both groups.
These data confirm findings of a previous trial20 and
emphasize the safety and efficacy of use of paracetamol
in the intrapartum period.
It is important to tailor intrapartum analgesic
methods used to the protocols of units, woman’s
wishes, needs and circumstances, such as anticipated

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Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology

duration of labor, the infant’s condition and cost.
i.v. paracetamol seems to be an effective and safe
analgesic, of reasonable cost and requiring no skill in
administration.
Acknowledgment
Thanks to Pharma Tech (Cairo, Egypt) for supplying
the used medicines (paracetamol and sterile water) in
the study.
Disclosure
All the authors declare no conflict of interest. The medi-
cines used (paracetamol and sterile water) in the study
were donated by Pharma Tech (Cairo, Egypt), with no
financial support provided to the authors or the work.
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