Diclofenac versus Pentazocine Hydrocloride for analgesia in first stage labor: a randomised controlled trial

¹Department of Obstetrics and Gynaecology, Alex Ekwueme Federal University Teaching Hospital, Abakaliki Ebonyi State, Nigeria, ²Department of Obstetrics and Gynaecology, Nnamdi Azikiwe University Teaching Hospital Nnewi, Anambra State, Nigeria

^&Corresponding author
Osita Samuel Umeononihu, Department of Obstetrics and Gynaecology, Nnamdi Azikiwe University Teaching Hospital Nnewi, Anambra State, Nigeria

Introduction    

The first stage of labor is the period from the onset of uterine contractions to the achievement of full cervical dilatation [1]. Parturient experience excruciating labor pain [2] which has both emotional and psychological impacts on women, their families, and caregivers. Labor pain is conveyed by spinal nerve segments T10 -L1 results from ischaemia of the uterus, effacement, and dilation of the cervix during contraction [1-5], may result in actual or potential tissue damage [6,7]. It is regarded as one of the most severe forms of pain and discomfort experienced by a woman in her lifetime [2,8-10]. The perception of labor pain perception varies among women [2,3,10-13] and may range from feeling of little pain to extremely distressing pain [2]. As a result, effective utilization of labor analgesia is a major concern for pregnant women and their families and has implications on the course of labor, the best results, and the quality of obstetric care [4,14-16]. Controlling pain during labor is believed to provide greater satisfaction rather than its total elimination, with its impact on overall satisfaction increasingly recognized in the last few decades [3].

Many methods of pain management during labor have been tried over the years. These include non-pharmacological and pharmacological methods of analgesia [3,6]. Nonpharmacological methods include psychoprophylaxis, hypnosis, and natural childbirth that emphasized the reduction of tension to induce relaxation [1, 3,6,17]. Pharmacological methods include inhalational analgesia, regional analgesia, and nonregional analgesics (opioids and nonopioids). Epidural analgesia is the most effective Labor analgesia [16,18] and is considered the gold standard [6, 9, 19,20]. Unfortunately, this method is not routinely available in most obstetric units in developing countries [21] for reasons of cost and personnel that lead to the use of systemic opioids for labor analgesia [6,22]. Opioids are inexpensive, easy to use and readily available [16]. One of the opioids, pethidine remained popular in many obstetric units [3,16,20,23,24] despite its safety concerns [20,24]. Maternal side effects include nausea, vomiting, sedation, respiratory depression, and delayed gastric emptying [24].

Pethidine also produces significant neonatal respiratory depression with behavioral and feeding problems that occur up to six weeks after delivery. All these adverse effects of pethidine led to the search for an equally potent but safer systemic opioid analgesic. The two commonly used opioids in Nigeria are tramadol and pentazocine [24]. Although safer than pethidine, these two are also associated with significant maternal and neonatal side effects [13,24]. The use of pentazocine in the advanced first stage of labor is associated with neonatal respiratory depression. However, this side effect can be managed by adequate neonatal resuscitation and use of naloxone [16]. There are also few trials of systemic non-steroidal anti-inflammatory drugs (NSAIDs) in the management of labor pains. Intramuscular Ketorelac [25], intravenous Tenoxicam [10] and intramuscular diclofenac [6] have been tried as analgesics in the management of pain in the first stage of labor. Whereas ketorolac was found to be less effective in labor pain control, it was found to be safer with fewer maternal and neonatal side effects compared to pethidine (opioids) [25].

Tenoxicam was found to be more effective than pethidine with no apparent maternal or neonatal side effect [10]. Diclofenac, on the other hand, was found in a placebo controlled trial to be effective in controlling labor pain and also lacked the adverse maternal and neonatal side effects associated with systemic opioids [6]. When given as a single dose, diclofenac has an analgesic effect and both analgesic and anti-inflammatory effect when full dose is given [23]. It is given once or twice daily by deep intramuscular injection. Currently, there are few studies that compare the efficacy of opioids and NSAID in labor pain management [6,10,24,25]. Therefore, this study compared the efficacy of intramuscular pentazocine and intramuscular diclofenac in the control of pain in the first stage of labor with the objective of providing an alternative labor analgesic that is devoid of the known side effects of pentazocine and other opioids.

Methods     

Study design: this was a randomised controlled study conducted in the labor ward unit of the Department of Obstetrics and Gynecology, AEFUTHA, and the labor ward unit of the St. Patrick's Mile 4 hospital Abakaliki. This was a randomized controlled double-blind study on the efficacy of IM diclofenac versus IM pentazocine as labor analgesia in the active phase of the first stage of labor. It is a clinical equivalence design.

Study setting: Ebonyi State is one of the five states in the southeast geopolitical zone of Nigeria. It has an estimated population of 2,176,947 million people who are predominantly of the Igbo ethnic group. Ebonyi State has a land mass of 6400 km², sharing boundaries in the west with Enugu state, Cross-river in the south, and Benue state in the north. AEFUTHA, Ebonyi State, is a tertiary health institution in the state capital. It is a referral center and the only teaching hospital in the state. It has 11 clinical departments, including the Department of Obstetrics and Gynecology. The Department of Obstetrics and Gynecology has 5 units. Each unit has two subunits manned by at least three consultants and 6 resident doctors, nurses, and midwives. The department runs her antenatal clinics from Monday to Friday each week. On average 60-80 patients are seen daily and 350-400 per week. In 2018, the total in-hospital delivery was 1953 of which 1625 were vaginal deliveries with an average of 135 vaginal deliveries per month. St. Patricks Mile 4 Hospital is one of the mission hospitals in the state. It was established in 1964 by the late Bishop MC-Gettrick initially to care for pregnant leprosy patients but later expanded to provide general maternal and child health services. It is managed by consultant obstetricians, medical officers, midwives, and resident physicians who are routinely posted from AEFUTHA. The annual delivery rate as of December 2018 was 2790 of which 1973 were vaginal deliveries with an average monthly vaginal delivery rate of 164.

Study participants: these comprised women of reproductive age at term with a singleton fetus who are undergoing vaginal delivery without contraindication to the use of diclofenac or pentazocine and gave informed consent to participate in the study during the antenatal period at 37 weeks gestational age and later presented in an active phase of labor. The study population was term-term pregnant women who received prenatal care in these facilities and gave their informed consent to participate in the study.

Inclusion criteria: the women included in the study were women diagnosed with a singleton fetus in active phase labor and who were previously selected booked primigravidae and multiparous women (Para 1-4) with a term pregnancy admitted to the labor room with cervical dilation of 4-7 cm.

Exclusion criteria: the excluded patients were unbooked pregnant women, women with medical diseases such as diabetes mellitus, hypertension, cardiac diseases, chronic renal disease, peptic ulcer disease, bleeding disorder, bronchial asthma, grandmultiparity, previous history of uterine scars, and opioid addiction.

Trial drugs

Pentazocine hydrochloride: pentazocine is a derivative of benzomorphan, with strong analgesic and weak narcotic antagonist activity [16,26], with both agonist and antagonist action at opioid receptors. It has no anti-inflammatory or antipyretic function [27]. Pentazocine reaches the peak analgesic effect in 1 hour of intramuscular administration, 15 minutes of intravenous administration, and in 1 to 3 hours of oral administration [26]. It is well absorbed by all common routes of administration, but the blood levels show considerable individual variation. The plasma half-life of pentazocine is approximately 2 hours after intravenous or intramuscular administration [26]. The use of pentazocine in the advanced first stage of labor is associated with neonatal respiratory depression. However, this side effect can be managed by adequate neonatal resuscitation and use of naloxone [16].

Diclofenac sodium: diclofenac sodium is an NSAID. It is a non-selective cyclooxygenase (COX) inhibitor. COX is the key enzyme in the prostaglandin synthesis pathway and exists in two isoforms, COX-1 and COX-2. Diclofenac inhibits both COX-1 and COX-2 and, like other NSAIDS, inhibits prostaglandin synthesis and release. In vitro, it inhibits neutrophil-endothelial cell attachment, which is a critical step in the inflammatory response. This effect is attributed to the rapid reduction in L-selectin expression on the neutrophil surface [28]. In a single dose, diclofenac has an analgesic effect, and in a regular full dose, it has both analgesic and anti-inflammatory action [23]. For acute pain, it is given once or twice daily by deep intramuscular injection [28]. The use of diclofenac and other NSAIDS in the third trimester of pregnancy has been associated with premature closure of the ductus arteriosus in the fetus. However, this side effect occurs when the interval between NSAIDS administration and delivery of the baby is at least 48 hours [26].

Sample size: the minimum sample size was determined using the RCT equivalence formula for equivalence RCT below [29].

N= sample size per study arm P= the response rate of the standard treatment group which was 0.25 (derived from a previous study) [6], = Standard normal deviation at 5% type 1 error =1.96, = Standard normal deviation at 80% power = 0.845, 0 = a clinically acceptable margin set at 10%.

Therefore, sample size per group =295, 10% of the minimum sample size per group (30) was added to correct for any attrition, so the final sample size was 325 for each arm given a total of 650 participants.

Patients´ recruitment: participants who were previously selected for the study gave their informed consent during the antenatal period at 37 weeks gestational age and presented in labor were evaluated to confirm age, parity, gestational age, number of fetus, presentation and position, and cervical dilation. The revalidation of consent to participate in the study was carried out in the labor ward. Those who still met the inclusion criteria were re-educated on the method of pain assessment using the visual analog scale (VAS). Randomization was performed using computer-generated random numbers in blocks of four. The trial drugs were placed in identical 2ml syringes with randomization codes in sealed, opaque, sequentially numbered envelopes. Participants were assigned to receive an intramuscular injection of diclofenac 75 mg or an intramuscular injection of pentazocine 30 mg by selecting the next number from sequentially numbered envelopes containing the trial drugs. The participant's data were extracted and the maternal vital signs (pulse, blood pressure, respiratory rate) were checked by the researcher or one of the trained research assistants and recorded in the data extraction form, and the labor pain was then assessed using VAS. Following the pain assessment, the next numbered envelope was opened, and the concealed drug administered by the trained midwife. The envelopes used were then resealed and returned to the pharmacist who kept them until the end of the study when unblinding was performed. The researcher or the research assistant on the labor ward, unaware of the type of injection administered, assessed, measured, and scored the level of pain using the VAS 30, 60, and 120 minutes after injection of the trial drug. Scores of 1-3 represent mild pain, 4-7 represe moderate pain and >7 represents severe pain. Maternal side effects were recorded. Maternal sedation was scored as 0=alert, 1 = drowsy, and 2=asleep. The time interval from the next request for analgesia was noted. Intrapartum monitoring was performed using the partogram, fetal Doppler, and the recorded delivery time. The neonatal condition was assessed by pediatrician at 1^st minute and 5^th minute Apgar scores. Naloxone was used for the treatment of opioid-induced neonatal respiratory depression cases.

Blinding, randomization, and allocation of concealment

Blinding: packaging, sealing, and numbering of the drugs were performed by a senior pharmacist who did not participate in the study. 75 mg of diclofenac in 2 ml of larger transparent ampoule and 30 mg of pentazocine in 2 ml of a smaller transparent ampoule were withdrawn in 2 ml syringes and labeled with appropriate randomization codes. This blinding was carried out every Sunday night in batches of 20 for each study center comprising 10 doses of each trial drug that is discarded after one week.

Randomization: a set of six hundred and fifty unique 4-digit random number codes comprising 325 even numbers and 325 odd numbers was generated by a statistician using the software Research Randomizer®. Even numbers were assigned to group A (the IM Diclofenac group) while odd numbers were assigned to group B (the IM pentazocine group). The drugs withdrawn in 2 ml syringes labelled with the randomization number codes were packaged in one envelope numbered 1 650 and sealed. These randomization number codes were only known to the senior pharmacist who kept them secret until the end of the investigation. Both the randomization number codes and the serial number on each of the envelopes were recorded and kept by the pharmacist. Unblinding was done after statistical analysis.

Allocation of concealment: the concealment allocation was performed by assigning the next participant to receive the trial drug in the next numbered envelope from 1-650. The sealed envelopes in each batch were kept in a designated locker that was easily accessible to the members of the research team.

Data collection: a total of 631 participants, including 394 from St. Patrick´s Mile 4 Hospital and 237 from AEFUTHA, completed the study. In presentation in active phase of labor on the labor ward of the two study centers with cervical os dilation of 4-7 cm, a structured pro forma was used to collect data from each of the participants. Data included sociodemographic characteristics and obstetric history. The protocol for labor analgesia in the two study centers includes the use of IM pentazocine 30 mg in the active phase of labor from 4-7cm cervical os dilation and IM tramadol 100 mg from 8 cm cervical os dilation. On request for analgesia, sealed envelopes containing the trial drugs were taken serially from 1-650. The unique randomization number codes on the drug given and the serial number on the envelope were recorded on the structured form, and the used envelopes were resealed and returned to the pharmacist who kept them until the end of the study when un-blinding was done. Assessment of the severity of labor pain was done immediately before injection, 30, 60 and 120 minutes after injection of the trial drug using a VAS. Each participant was asked to place a perpendicular mark on the VAS line at the point that he felt represented his current intensity of pain. The mark was then measured from the left (no pain) end with a ruler to determine the score. Scores of 1-3cm = mild pain, 4-7cm = moderate pain and >7cm = severe pain. After delivery, the pediatrician present at delivery evaluated the neonates using the Apgar score at the first and fifth minute.

Study measurements

Primary outcome measures: the main outcome was the pain score recorded at 30, 60 and 120 minutes after injection of IM diclofenac 75 mg and pentazocine 30 mg.

Secondary outcome measures: maternal and neonatal side effects of diclofenac and pentazocine observed.

Statistical analysis: the collected data were tabulated and analyzed using statistical product and services solution software (IBM SPSS) (version 20, Chicago II, USA). Analysis was done to treat. Quantitative variables were presented as mean and standard deviation (mean ± 2SD), while categorical variables were presented as numbers and percentages. The Chi-square test (or Fisher's exact test where applicable) and the Mann-Whitney U test were used for comparison between groups for categorical variables and the t-test for comparison between groups for continuous variables. A difference with a value of P <0.05 was considered statistically significant.

Ethical considerations: permission to carry out this research was sought and obtained from the AEFUTHA Research and Ethics Committee (FETHA / REC / VOL2/2019/284) and St Patrick´s Mile 4 Hospital Abakaliki (RE/M4H/59/20). The trial was registered with the Pan African Clinical Trial Registry (PACTR202212654526624). Each participant signed a consent form at 37 weeks gestational age and revalidated in labor after adequate information concerning the purpose of the study objectives, procedure, risk, discomfort, and potential benefit. Participants were made to understand that declining participation will not affect their care.

Results     

During the study period, a total of 650 participants were recruited from the antenatal clinics at 37 weeks of gestation and consent to participate in the study was obtained. However, of this number, a total of 631 participants comprised 317 and 314 in the diclofenac (group A) and pentazocine (group B) groups, respectively, presented in labor at the 2 hospitals and participated in the study (Figure 1). Table 1 shows the sociodemographic characteristics of the participants. There were no statistically significant differences in sociodemographic characteristics between study participants (P> 0.05). There was no significant difference between weight, height, and BMI of study participants in the two groups (P>0.05).

Table 2 and Table 3 show the efficacy of trial drugs as assessed using the visual analog scale and analgesic requirement. On admission and before the administration of the trial drug, 286 (90.2%) participants in the diclofenac arm 226 (72.0%) participants in the pentazocine arm had severe pain while 31 (9.8%) participants, and 18 (5.7%) participants in the diclofenac and pentazocine arms respectively had moderate pain. There was no significant difference in pain rating between nulliparous women and Para 1-4 (P>0.05). At 30 minutes after administration of the trial drugs, the number of participants with severe pain decreased from 90.2% to 48.6% in diclofenac and from 72.0% to 49.0% in pentazocine groups, respectively, while the number of participants with moderate pain increased from 9.8% to 51.4% in diclofenac and from 5.7% to 51.0% in pentazocine groups, respectively. At 60 minutes, the number of participants with severe pain reduced from 90.2% to 23.0% in diclofenac and from 72.0% to 17.8% in pentazocine groups respectively, while the number of participants with moderate pain increased from 9.8% to 76.0% in diclofenac and from 5.7% to 79.9% in pentazocine groups respectively.

The number of participants with mild pain also increased from 0.0% to 0.9% in the diclofenac groups and from 0.0% to 2.2% in the pentazocine groups, respectively. There was no significant difference in pain reduction between the two arms and between nulliparous women and Para 1-4 (P>0.05). At 120 minutes, the number of participants with severe pain reduced from 90.2% to 19.2% in diclofenac and from 72.0% to 15.9% in pentazocine groups, respectively, while the number of participants with moderate pain increased from 9.8% to 80.8% in diclofenac and from 5.7% to 81.5% in pentazocine groups, respectively. The number of participants with mild pain also increased from 0.0% to 3.2% in the diclofenac groups and from 0.0% to 2.5% in the pentazocine groups, respectively. There was no significant difference in the pain score at 30 minutes, 60 minutes, and 120 minutes after drug administration between the two groups (P>0.05).

At 30 minutes after the administration of the trial drugs, moderate/good pain relief was achieved in 59.3% and 67.5% of the participants who received IM diclofenac and IM pentazocine respectively, while none/mild pain relief was achieved in 40.7% and 32.5% of the participants who received IM diclofenac and IM pentazocine respectively. At 60 minutes, the number of participants in whom moderate/good pain relief was achieved increased from 59.3% to 81.1% and from 67.5% to 85.4% in the diclofenac and pentazocine groups, respectively, while those in whom none/mild pain relief was achieved were reduced from 40.7% to 22.1% and 32.5% to 14.6% in the diclofenac and pentazocine groups, respectively. At 120 minutes, the number of participants in whom moderate/good pain relief was achieved was 77.9% and 85.0% in the diclofenac and pentazocine groups, respectively, while those in whom none/mild pain relief was achieved were reduced from 40.7% to 22.1% and 32.5% to 15.0% in the diclofenac and pentazocine groups, respectively. The difference in pain relief achieved in both groups was not statistically significant (P<0.05). The mean time to the first subsequent request for analgesia was not significantly different between the two study groups (P>0.05) (Table 4).

Table 3 shows the maternal and neonatal side effects caused by trial drugs. Diclofenac was three times less likely to cause maternal drowsiness and sedation and two and half times less likely to cause vomiting than Pentazocine (RR=0.32, 95% CI (0.2-0.46). The two drugs did not have a significant effect on neonatal APGAR score at the first minute, APGAR score at the fifth minute, and admission to the NICU. Table 5 shows maternal satisfaction and dissatisfaction with the pain reliever achieved. The majority (96.0%) of the women expressed satisfaction with the level of pain control achieved with the trial drugs. Satisfaction was greater among parturients in the diclofenac group compared to the pentazocine group, although not significant (RR = 0.84 95%CI 0.60-1.18, P=0.323). The number of patients who needed to be treated with the test drug (diclofenac) was 10.5 for an additional patient to benefit. Intragroup analysis showed that nulliparous women who received diclofenac had more pain relief compared to those on the pentazocine arm; on the other hand, there are no significant changes in the level of pain relief perceived among multiparous women in both arms of the trial drugs. Multiparous women in diclofenac were more satisfied compared to primiparous women (RR = 0.91 95% CI 0.80-1.03, P = 0.148). Generally, maternal dissatisfaction with labor analgesia was more common with the cohort of women that received diclofenac compared to the control group (RR = 1.45 95%CI 0.64-3.30, P= 0.374).

Discussion     

Labor is a distressing condition associated with severe pain. Pain is the most common clinical complaint, causing great human suffering [30]. Providing pain relief for women in labor is important for maternal health [31]. Our study aims to evaluate the analgesic efficacy of intramuscular diclofenac (IM) in the first stage of labor compared to pentazocine IM. From Table 2, it is obvious that labor is associated with considerable pains in both nulliparous and multiparous women, although there is no significant difference in the initial assessment of pains between the groups. In our study, the majority of the study population assessed labor pain to be severe, which is consistent with the work of Obuna et al. in the study area [2] and other previous studies [6]. Labor pain needs to be markedly reduced to improve maternal satisfaction with the labor process [31,32]. Various studies have tried different pharmacological agents for labor analgesics with different efficacy. Among the methods, systemic opioids, non-opioids, epidural analgesia, combined spinal-epidural analgesia, and inhalation agents are used to manage labor pain [31]. Epidural analgesia is the best and provides almost complete relief from labor pain. In similar studies among women during childbirth, the efficacy of non-steroidal anti-inflammatory drugs in reducing the level of pain has been reported [6,33,34,35].

In our study, there is an increasing number of women with labor pain relief after the administration of trial drugs. None of the women reported severe pain, and a more beneficial effect of the agent used was observed in multiparous women compared to the nulliparous group [36]. Thus, this finding highlights the beneficial role of drugs in labor pain among the study population, unlike the work of Obuna et al. who reported on the severity of pain experienced by mothers during childbirth [2]. Although not significant, the administration of IM diclofenac during labor is associated with better relief from labor pain compared to the use of IM pentazocine. Rescue analgesics was more on IM pentazocine group. The finding can be attributed to the lower efficacy of pentazocine hydrochloride as a labor analgesic compared to diclofenac. Diclofenac, a NSAID, has been reported to have a positive effect on the mechanism of uterine pain. Labor pain during the first stage of labor is mainly attributed to cervical dilation and uterine contractions, of which diclofenac is effective in relieving pain originating from uterine contractions during labor, unlike opioids [34]. This probable benefit of diclofenac might be of considerable advantage in labor care due to the lack of neonatal depression, which is a potential confounder with pentazocine administration. Although neonatal depression was not observed in our study, its non-occurrence in our study could be related to the timing of pentazocine administration. In our study, it was administered remote from neonatal delivery, therefore not associated with neonatal depression.

In Table 3, pentazocine hydrochloride is associated with an increase in maternal side effects such as nausea, vomiting, and maternal sedation. This finding is consistent with previous studies on the use of opioids during childbirth [36,37,38]. IM Diclofenac might be a better choice due to its better profile of maternal side effects. The safety of IM diclofenac in this study was similar to the findings in previous studies by Shalaby et al. [10] in which tenoxicam (an NSAID) was compared with pethidine. In our study, the fetal Apgar scores in the first and fifth minutes were not significantly affected by the trial drugs. Pentazocine is known to cause neonatal respiratory depression, increasing the risk of admission to the NICU. The use of opioids has been reported to cause fetal metabolic acidosis, and is most marked with pentazocine [39]. Thus, caution is required on its use, especially in low-resource settings where the availability of adequate neonatal resuscitative measures might be lacking. In the index study, fetal and neonatal blood gases were not evaluated, and we cannot infer the probability of such abnormality in our newborns.

Maternal satisfaction as described by the Donabedian model is anchored on three dimensions of the categories 'structure', 'process', and 'outcomes' [32]. The process is the healthcare provided and, for a pregnant woman, is the overall care received in labor. Appropriate labor analgesia is necessary to increase maternal satisfaction with labor [32]. The majority of women we studied expressed satisfaction with the level of pain relief that occurred with the trial drugs. Maternal satisfaction with labor analgesia is higher among the cohort of women in the diclofenac IM diclofenac group than in the pentazocine IM arm, although not significant. The utilization of obstetric analgesia is very low in sub-Saharan countries [2,40,41] and this poor utilization is influenced by factors such as the non-availability of effective drugs, fear of potential maternal and neonatal side effects, lack of knowledge of the obstetric caregiver and the obstetric population about labor analgesia, and the positive attitude and experience of the obstetric caregivers were factors significantly associated with the use of labor pain relief methods [37,40,41]. The high number of women in our study who express satisfaction with labor analgesia is a wake-up call for labor managers in our environment to make it (labor analgesia) available to pregnant women in the study area. The discovery that IM diclofenac is effective as labor analgesia with a good safety profile has increased the number of effective drugs available as labor analgesia in the study area.

Limitations of the study: assessment of labor pain was made using VAS with its subjective nature. This may have affected the study results due to desirability bias. However, effort was made to reduce its occurrence by proper counselling of the study population on the need to truly represent the level of pain felt. The study population was also well-educated on VAS. Our study is a single-center study with bias, and our findings could not be generalized to the obstetric population in the study area. We recommend a multicenter study involving other hospitals in the state to help authenticate our findings. Due to the small sample size used in this study, it may not have been able to detect side effects for universal applicability. The fact that unbooked patients were excluded from the study also limits its universal applicability.

Recommendation: this study found intramuscular diclofenac to be as effective as pentazocine but with less side effects when used in the management of labor pain. However, more studies are needed before recommending IM diclofenac as an alternative to IM pentazocine for use in the management of pain in the active phase of the first stage of labor.

Conclusion     

According to our study, IM diclofenac 75 mg is as effective as intramuscular pentazocine 30 mg when used in labor pain management in the active phase of the first stage of labor. Its use in this study was not associated with any serious maternal or neonatal side effect.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

Philip Chidiebere Osuagwu and Chidebe Christian Anikwe: conceptualization/study design, data collection/analysis, and interpretation of findings, and drafting and writing of the manuscript. Osita Samuel Umeononihu. Ayodele Obianuju Okwuosa, Darlington-Peter Chibuzor Ugoji, Ikenna Chidi Ebere and Ayodele Adegbite Olaleye: data collection, interpretation of findings, and drafting of the manuscript. All the authors have read and agreed to the final manuscript.

Tables and figure     

Table 1: sociodemographic characteristics of the patients

Table 2: analgesic effect of the trial drugs as evaluated by VAS on pain during labor

Table 3: analgesic effect of the trial drugs as evaluated by VAS on pain relief during labor

Table 4: maternal and neonatal side effects

Table 5: maternal satisfaction with the analgesic effect of the trial drug

Figure 1: the flow of study participants during the study period

References