The present single-centre, single blind, randomized parallel assessment trial was conducted in Department of Obstetrics and Gynaecology in Vardhaman Mahavir Medical College & Safdarjung hospital over a period of six months from September 2014 to March 2015 after getting ethical clearance. Subsequently, after taking a written informed consent, the first 200 consecutive women in labour presenting for delivery at the institute, fulfilling the following inclusion criteria were recruited into the study: a) primiparous low-risk parturients; b) aged 18–35years; c) spontaneous onset of labour at term (37–42 weeks gestation); d) First stage of labour with cervical dilatation of 3–6 cm; e) single viable fetus; f) cephalic presentation; g) patient seeking analgesia. The exclusion criteria were: a) clinical evidence of cephalo-pelvic disproportion; b) malpresentation; c) any medical disorder during pregnancy; d) induction of labour; e) use of any other kind of analgesia before recruitment to the study; f) scarred uterus; g) fetal distress; h) Antepartum Haemorrhage (APH); i) Intrapartum bleeding; j) Polyhydraminos; k) Prelabour rupture of membranes(PROM); l) Intrauterine infection; m) Postpartum Haemorrhage (PPH); n) Previous history of hypersensitivity to paracetamol.

Among 960 women scrutinized, 200 fulfilling the inclusion criteria were enrolled in the study after excluding 760 females. Cervical dilatation and demographic data, including age, gestational age, and body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters), were recorded.

The sample size was calculated using the latest available via Epi Info version to obtain a power (β) of 80% and a significance level (α) of 0.05. Analysing the body of work on labour analgesia, a minimal sample size of 100 women in each group was needed to observe the optimal confidence interval. After conscription, each participant was randomly allocated to either of the two Groups A or B by a concealed sequence of a computer-generated randomization plan.

The participants in Group A (Cases, n=100) received a 100-mL intravenous infusion containing 1000 mg of acetaminophen (Paraglan-IV, Gland pharma limited, Hyderabad, India) over 15 minutes; in group B (Controls, n=100), women received an intravenous infusion of 100 mL of normal saline (NS, Albert David limited, Ghaziabad, UP, India) over 15 minutes. Labour was followed up according to the hospital’s protocols with artificial rupture of membranes and subsequent augmentation with an oxytocin infusion (if there were fewer than 3 contractions in 10 minutes, each lasting less than 40 seconds). Parturients described pain intensity on a 100-mm VAS, delimited by “no pain” and “the worst pain”, just before having obtained the study drug and subsequently at 15 minutes, 1 hour, 2 hours, 3 hours and 4 hours after drug administration. Pain assessment was performed by intern (who had no role in patient enrolment and was blind to the drug administration). Women who did not deliver within 4 hours and still needed analgesia were given an additional injection of tramadol intramuscularly 50mg (Pentazen, Ind Swift Limited, Najabgarh, India) in both the groups. All the drugs used were available free in hospital supply. Pain was not assessed after 4 hours because, despite the possibility of repeated drug intake, by then more than 50% of participants had delivered—either vaginally or by caesarean. This would lower the participant numbers and shorten the interval to delivery, making the comparison non-informative.

The primary outcome measured were efficacy of the drug to supply adequate analgesia, as measured by a change in the VAS pain intensity score at 15 minutes, 1 hour, 2 hours, 3 hours and 4 hours after drug administration. Secondary outcome measures included duration of labour, need for rescue or additional analgesia, and presence of maternal uneasiness or adverse effect (dizziness, tachycardia, dyspnoea, vomiting, blurred vision, dryness of mouth, and significant changes in blood pressure {≥30 mm Hg systolic or ≥15 mm Hg diastolic}) and fetal/ neonatal adverse events (non-reassuring cardiotocography including foetal tachycardia, low Apgar scores at 1 and 5 minutes, and need for admission to the intensive care unit).

Data was recorded on a predesigned proforma and deciphered at end of study using relevant statistical tests. Excel 2010 (Microsoft, Redmond, WA, USA) and SPSS version 18.0 (IBM, Armonk, NY, USA) were used for data presentation and statistical analysis.

Parturients in both the groups were primigravidae in active stage of labour and were comparable to one another in their demographic characteristics [Table/Fig-1]. Women in both the groups had comparable VAS scores before the initiation of treatment (6.82-7.34 in Group A and 6.76-7.28 in group B) [Table/Fig-2]. In contrast to the pretreatment score, the mean VAS score was lower at 15 minutes, 1 hour, 2 hour, 3 hours and 4 hours after treatment in both groups. The lowest scores were observed at 2 hours of drug administration. Comparing the change in VAS score from the initial score between the two groups, the reduction in pain was significantly greater in Group A at all times except at 15 minutes. [Table/Fig-2]. No variation in mean drug-to-delivery interval was noted (paracetamol group, 3.6 hours; placebo 3.5 hours) [Table/Fig-3] in both the groups. No variance in the percentage of vaginal deliveries (94% each) was observed in either of the groups [Table/Fig-4]. Lower Segment Caesarean Section was performed in six subjects each in both the groups due to non-reassuring fetal heart rate patterns. No adverse maternal or neonatal effects were witnessed in either groups. There were no differences in the occurrence of intrapartum fetal distress or lowered neonatal Apgar scores between both groups [Table/Fig-5].

Pain relief during labour has been exemplified to have a positive bearing on its course [15]. During the last two decades, obstetric analgesia and anaesthesia have evolved from an ambiguous probability to actuality. Amongst pharmacological approaches, although central neuraxial analgesia is considered the criterion standard, a number of parturients may still be reluctant to have regional analgesia [4]. Also, it entails participation of skilled anaesthesiologist, expensive paraphernalia and incessant monitoring amenities that cannot be made routinely accessible in developing countries like India, where a major chunk of obstetric services is still rendered by midwives, trained nurses and non-specialist doctors at grassroots levels. An effective substitute may be the utilization of parenteral opioids with a relative ease of administration [16]. But marked side effects restrict their liberal use for the same. This propelled exploration for role of IV acetaminophen as intrapartum analgesic.

Observations of the present study lucidly demonstrate that use of IV acetaminophen injection for intrapartum analgesia is superior to placebo, as determined by the considerable drop in VAS score from 15 minutes and one hour and a statistically significant reduction in pain at 2 hours, 3 hours and 4 hours in comparison to the pretreatment VAS pain score. These results were better than the research of Lallar et al., and Elbohoty et al., involving IV acetaminophen, thus establishing it as a feasible option for labour analgesia [17,18]. However, the high pre-treatment pain scores amongst the participants in our study may be explained by recruitment of women in active labour who were deemed in need of analgesia.

Unlike the past pollsters [18], the mean VAS in the concurrent study after 2 hours was always lower than the pre-treatment scores, and this effect lasted for 4 hour giving us reassuring data about the duration of effectiveness of acetaminophen.

Akin to the research done there was no difference in the mean drug to delivery interval between the two groups, although there was some shortening effect than the usual anticipated duration of 4 to 6 hours [19]. This could be attributed to the positive influence of analgesia on maternal bearing down efforts and progress of labour. However, these results were different from those obtained by few recent studies [17,20]. The possible reasons could be the non-recording of dose and mean duration of administration of oxytocin by those investigators, besides lack of adequate power in those studies. Nevertheless, this role of acetaminophen in shortening the drug delivery interval needs to be reconnoitred in future on a larger scale.

In our study, only 16% women required rescue shot of analgesia, further reinforcing the efficacy of acetaminophen as intrapartum analgesic.

Analyzing mode of delivery, no variance in the percentage of vaginal deliveries (94% each) was observed, with 6 subjects in each group undergoing LSCS due to non-reassuring fetal heart rate patterns [Table/Fig-4]. There was no instrumental vaginal delivery in either group. These findings corroborated those witnessed by most of the canvassers [17,18,21].

Absence of any maternal adverse effects (sedation, respiratory depression, delayed gastric emptying, nausea and vomiting) or neonatal adverse effects (respiratory depression and decreased Apgar scores) associated with opioids in the current study further bolstered liberal use of acetaminophen to alleviate labour pain [18–21]. Passable assessment of pain, utilizing authenticated tools apposite to the study population is an indispensable prerequisite of successful analgesia. A Numeric Rating Scale (NRS) with numbers from 0 to 10 (‘no pain’ to ‘worst pain imaginable’) has off late emerged as more practical and easier to understand than a VAS, in assessing pain relief in women especially with difficult communication or patients suffering from cognitive impairment [22,23].

All the aforementioned findings thus validate IV acetaminophen to be an effectual and innocuous intrapartum analgesic, of equitable cost and requiring no proficiency in dispensation.

There are certain limitations of this study. Firstly, having been drawn from a moderately small study populace of 200 women over a short span of six months, the aforesaid results may not be representative of the initial promising results in other settings. Thus, larger powered studies with larger size of study population are recommended to precisely elucidate the analgesic profile of intravenous acetaminophen in labour. Secondly, in the present study, there was no statistically significant shortening on the duration of labour caused by acetaminophen. This could be ascribed to women enrolled into the study with a relatively wide range of cervical dilatation of 3-6 cm. A further breakup of this parameter to compare the effect of drug on labour duration between ≤4cm and ≥5cm dilatation of cervix on administration could cause enhanced enrichment of the investigators with respect to it in order to justify its use for this purpose. Thirdly use of NRS might have enhanced our results even further in favour of acetaminophen.

Intravenous acetaminophen is an efficacious non-opioid drug for relieving labour pain without any maternal and fetal adverse effects. It shortens the duration of labour. However, further larger studies comparing acetaminophen infusion with opioid analgesics are recommended to confirm these findings. Also, the effect of acetaminophen in reducing duration of labour is beguiling and necessitates future research, with potential benefits being, a) a lower incidence of complications associated with prolonged labour (neonatal sepsis or maternal infection such as chorioamnionitis or puerperal sepsis); b) advantageous in diminished foeto-placental reserve, reducing the incidence of abdominal delivery; c) Reducing the time of parturition would be welcomed by women and by health authorities with limited medical resources especially in low-income countries.