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doi: 10.1093/bja/aew311
Obstetrics
OBSTETRICS
Abstract
Background: Use of i.v. paracetamol for postoperative pain is well documented, but it is unclear if it can reduce the con-
sumption of opioids during patient-controlled epidural analgesia (PCEA) in labouring parturients.
Methods: In this randomized, double-blind, placebo-controlled clinical trial conducted in a tertiary care hospital, 80parturi-
ents were randomly assigned to two groups of 40 each, to receive either 1000 mg (100 ml) i.v. paracetamol or 100 ml normal
saline as placebo, 30 min before the procedure. After insertion of the epidural catheter, all patients received 10 ml of levobu-
pivacaine 0.1% with 2 lg ml-1 fentanyl, followed by continuous background epidural infusion of 6 ml h-1 with a provision of
patient-controlled bolus 5 ml of same drug with a lock-out interval of 12 min.
The primary outcome was hourly mean consumption of levobupivacaine and fentanyl mixture (ml.h-1). Secondary
outcomes included pain score, sensory and motor block, haemodynamic parameters of mother, duration of second stage of
labour, mode of delivery, Apgar scores, foetal heart rate and adverse effects.
Results: The hourly mean drug consumption in the Paracetamol group was significantly lower as compared with the
Placebo group (7.03 ml.h-1, SD 0.83 vs. 8.12 ml.h-1, SD 1.34; p < 0.001). The mean number of boluses taken were also
significantly less in the paracetamol group (1.00, SD 0.93 vs. 1.43, SD 0.90; p 0.036). Pain scores decreased in both the groups
without significant inter-group differences.
Conclusions: Use of 1000 mg i.v. paracetamol decreases the mean hourly drug consumption through epidural route. Thus
i.v. paracetamol is a safe and effective adjunct to PCEA in labour analgesia.
Clinical trial registration: Clinical Trials RegistryIndia (http://ctri.nic.in/Clinicaltrials/login.php), trial registration number
2013/09/003968.
Key words: administration, intravenous; analgesia; analgesia, epidural; obstetric labour; paracetamol; patient-controlled
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618 | Gupta et al.
(n=92)
Excluded (n=12)
clinically). All these variables were recorded every 5 min for the value of 12.4 ml h-1 as the mean hourly neuraxial drug con-
first 20 min and then every 1 h until delivery. Duration of second sumption in the paracetamol group.
stage of labour, mode of delivery, Apgar scores and maternal Thus, for this study, sample size analysis with the above
satisfaction (VAS) were also recorded at the end of labour. assumption and with b of 0.20 (i.e. power of 80%) and a of 0.05
Women were questioned regarding their satisfaction for analge- demonstrated that a sample size of 36 per group would allow us
sia and future desire to use it in subsequent pregnancies, to detect a 20% difference in total epidural drug combination
12-24 h after delivery, using separate 100 mm visual linear ana- volume required per h. To allow for slight oversampling, it was
logue scales. decided to have a total sample size of 80 patients, with 40
patients per group.
Table 1 Comparison of patient characteristics in the two groups Table 3 Comparison of mode of deliveries (MOD) in the two
groups
Characteristics GROUPI GROUPII
(PCM) N 40 (PLACEBO) N 40 MOD Group I Group II P value
(PCM) n40 (PLACEBO) n40
Age (yr) 26.15 25.9
Range 20-35 21-32 Normal n (%) 29 (72.5) 30 (75) 0.799
Height (cm) 157.55 (4.43) 157.6 (5.21) Forceps assisted n (%) 5 (12.5) 3 (7.5) 0.456
Mean (SD) Caesarean n (%) 6 (15) 7 (17.5) 0.762
Weight (kg) 66 (9.89) 69.18 (11.79)
Mean (SD)
ASA I Category 39 (97.5%) 39 (97.5%)
n (%)
Regarding the primary outcome of interest, it was seen that Adverse effects were common but minor in this study and con-
the mean hourly drug consumption was significantly lower in sisted mainly of nausea, vomiting and urinary retention. There
the paracetamol group (7.03 ml, SD 0.83; range 5.77-8.75) as com- were non-significant differences in occurrence of side-effects
pared with the placebo group (8.12 ml, SD 1.34; range 6.00-11.70; between the two groups (Table 5).
P <0.001). The paracetamol group also required significantly less
total number of boluses (mean 1.00, SD 0.93; interquartile range
[IQR] 0-2) than placebo group (mean 1.43, SD 0.90; IQR 1-3;
Discussion
P 0.036). When hourly bolus consumption rate was compared, This randomized, double-blinded, placebo controlled clinical
statistically significant difference in the bolus consumption was trial demonstrated that i.v. paracetamol is a safe and effective
observed at 2 h, with lower bolus consumption in the paraceta- adjunct to PCEA in labour analgesia. A few previous studies
mol group as compared to placebo group. No significant differ- have shown the effective use of i.v. paracetamol during intra-
ence was found in number of boluses taken at the rest of the partum period.918 Elbohoty and colleagues9 showed that use of
time intervals over the study period. i.v. paracetamol, was as effective as pethidine for intrapartum
In our study, time to onset of analgesia was recorded from analgesia during the first stage of labour. In another study done
the time when the bolus drug was injected, to the time when by Abd-El-Maeboud and colleagues10, it was demonstrated that
VAS became less than three. The mean onset time was similar i.v. infusion of paracetamol was associated with significantly
in both groups (11.90 min, SD 2.09 in paracetamol group and lower VAS score and lower incidence of need for rescue medica-
12.00 min, SD 1.93 in placebo group; 95% Confidence Interval [CI] tion as compared with sterile water (placebo) for intrapartum
of Difference of Means -0.998 0.798; P 0.82). The mean VAS analgesia. In both these studies, and in the recently published
score before institution of epidural analgesia was comparable in studies from Iran,11 India12,13 and USA,14,15 i.v. paracetamol was
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