A thought for tramadol hydrochloride as labor analgesic.

AIMS: To evaluate and compare the analgesic efficacy and adverse effects of tramadol and meperidine in labor. SUBJECTS AND METHODS: One hundred sixty-three of the 213 parturients at term in active labor were randomly assigned to one of three groups to receive intramuscularly either tramadol 50 mg (N = 54), tramadol 100 mg (N = 55) or meperidine 75 mg (N = 54). Single person who was not aware of the given drug (NS) assessed analgesic effect using visual analogue scale (VAS). Maternal side effects, effect on labor, and perinatal outcome were also studied. STATISTICAL ANALYSIS: Effect of the drugs used on maternal and fetal wellbeing was compared within study groups in reference to the control group. The quantitative analysis was done using unpaired t-test and for qualitative analysis chi-square test was applied.
RESULTS: Proportion of cases with satisfactory to good pain relief (VAS difference >5) after 2 h of administration was 35.2 (19 of 54), 61.8 (34 of 55) and 70.3% (38 of 54) in tramadol 50 mg, tramadol 100 mg and meperidine 75 mg groups, respectively. Nausea and/or vomiting (11% vs. 7%), drowsiness (20.4% vs. 5.5%) and fatigue (16.7% vs. 6%) were significantly high in meperidine than in tramadol groups (P<0.05). Proportion of cases with nonreassuring fetal heart rate and neonates with <7 Apgar were high in the meperidine group. Meconium stained liquor was seen equally in tramadol 100 mg and meperidine groups, and was lower in tramadol 50 mg group. All the intervention groups had relatively shorter observed active phase of labor than controls.
CONCLUSIONS: Tramadol 100 mg is an equally effective labor analgesic as meperidine with less maternal and perinatal side effects.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Pain in labor is unpleasant and distressing to the parturient. The relief of pain during childbirth and provision of a dignified birth experience has been of great interest both to the obstetrician and anesthesiologists.

An ideal analgesic in obstetrics should have potent opiate like, analgesic efficacy and possess minimal side effects. Psychological methods of pain relief in labor are time consuming, relief unpredictable, inconsistent, and incomplete. Physical methods like transcutaneous electric nerve stimulation, subcutaneous sterile water injection to the lower back, provide limited pain relief. Epidural analgesia is considered as gold standard for care because of good pain relief it provides. But its effect on progress of labor and mode of delivery remain debatable and its universal use is still limited probably due to lack of awareness, trained staff and monitoring facilities. Systemic opioid, meperidine (Pethidine) has been in use as labor analgesic for many years. However, the wide spectrum of unpleasant side effects and neonatal respiratory depression are the deterrents for its use. With the aim to reduce side effects and improve analgesia, many alternatives to meperidine have been under investigation.

Tramadol is one such weak opioid analgesic with analogous analgesic efficacy to meperidine, less maternal sedative effect and less neonatal respiratory depression.[1]

The present prospective comparative study was done to assess the analgesic efficacy, safety, and effects of one injection of tramadol in comparison with meperidine in active labor.

SUBJECTS AND METHODS

Following informed consent the study was carried out in 220 normal primigravidas in the active phase of labor at term, with singleton fetus presenting by vertex. Women with obstetric or medical complications and those with scar on uterus due to myomectomy or any surgery on uterus were not included.

Parturient was considered to be in the active phase of labor for recruitment, if she was getting at least three regular painful uterine contractions in 10 min and had cervical dilatation between 3-5 cm.

Women were allocated to three groups (Tramadol 50 mg, Tramadol 100 mg and Meperidine 75 mg) using computerized block randomization. Single dose of a particular analgesic was administered intramuscularly to the designated group in the deltoid region along with 25 mg of promethazine.

Parturient who were willing to participate in the study but not desirous to take analgesics were recruited as the comparative control group. No placebo was given to them. They were not denied pain relief if requested in the course of labor. Since the number was falling short of the required for study, women who went through labor without any analgesic help were also included in the control group.

Pain relief was assessed by visual analogue scale of 10 scores ranging from no pain to unbearable pain. Pain was assessed in the three study groups before administration of the drug, and every 30 min for 2 h and thereafter hourly for 2 h or full cervical dilatation, whichever was earlier. The assessment period of 4 h was chosen since it would approximate with the duration of analgesic action of both tramadol and meperidine. The person assessing the pain (NS) was blinded to the nature of analgesic given to the woman and did not take part in the parturient management.

Based on the mean visual analogue score difference, the responses at each assessment were categorized into four groups–good (7.5-10), satisfactory (5-7.5), mild (2.5-5) and nil (<2.5) for the purpose of the study. The pain scores of tramadol 50 mg group were compared with the other study groups.

Duration of active phase of labor was taken as duration of labor in control group. In study groups, analgesic injection-delivery interval was considered as duration of labor.

Neonatologist attending the delivery was informed of the drug given.

Effect of the drugs used on maternal and fetal wellbeing was compared within study groups in reference to the control group. The quantitative analysis was done using unpaired t-test and for qualitative analysis chi-square test was applied.

RESULTS

There were 213 women studied and analyzed for this effectiveness study. Five of the women in control group required analgesic in the course of labor. Similarly, a woman each in tramadol 50 mg and meperidine 75 mg groups required administration of additional analgesic doses. All these women were excluded from the study [Figure 1].

Figure 1

Distribution of cases in different study groups

Mean maternal age and weight, and neonatal weights were comparable in the groups studied [Table 1].

Table 1

Comparative age and weight of mother and neonate

Maternal systolic blood pressure (SBP), pulse rate, and respiratory rate were similar in different study and the control groups. The group receiving meperidine had significantly higher proportion of cases with effects of nausea and/or vomiting, drowsiness, and feeling of tiredness. When effect on fetal parameters was considered, number of cases with nonreassuring fetal heart trace and neonates with low Apgar scores, though not significant, was higher in meperidine group than in those with tramadol and control groups. Five neonates in the meperidine group required naloxone, while none from the tramadol groups. However, mean fetal heart rate and incidence of cases with meconium in liquor showed no difference between any of the groups studied [Table 2].

Table 2

Maternal and fetal-neonatal effects of single dose of opiate analgesic in labor

The drugs used did not appear to influence either the observed duration or mode of delivery. Number of women with vaginal delivery was higher in groups receiving tramadol than meperidine (P < 0.05). Women receiving tramadol 50 mg had similar instrumental vaginal and cesarean delivery rates as controls. The mean duration of labor was shorter in the tramadol and meperidine groups than in controls. Tramadol 100 mg and meperidine 75 mg groups had shorter labors than tramadol 50 mg group, and in them number of women delivering by 4 h was higher [Table 3].

Table 3

Effect on outcome of labor

The preanalgesic median visual analogue score of perception of pain was 8 in all the three groups. The calculated median pain perception scores did not show significant change between the groups with change in time. Based on individual pain perception scores, satisfaction level was calculated. Since the maximum analgesic action of these drugs is up to 2 h and wanes off by 4 h, only the results at these hours are shown. Number of women recording good to satisfactory analgesia was significantly lesser in tramadol 50 mg group than in the other study groups (P < 0.05). And nearly 25% of women receiving tramadol 50 mg indicated no relief at 2-h assessment [Table 4]. The average visual analogue scores and the number of women in each satisfaction levels remained similar.

Table 4

Perception of pain relief in labor after injection by different groups

DISCUSSION

Pain is the most important human experience and also is most complex. Pain experienced during labor is reported as severe or intolerable in up to 61% of women who went through labor. This discomfort may result in harmful physiologic responses in both the mother and fetus. In addition pain during childbirth may result in the experience being distressing and disappointing for the parturient.[2]

There are several methods and drugs used for relief of pain in labor. Though it provides a very effective analgesia, epidural administration remains the least utilized method in labor care facilities in countries like India because of dependence on availability of anesthesiologist, involved cost and monitoring. Meperidine, an opioid narcotic analgesic is the one in frequent use than the other injectable analgesics. Restrictions on its availability and sale because of scope for misuse, neonatal depression and unavailability of nalorphine when required combined with lack of awareness of its use by all levels of maternity care providers, make meperidine a less dependable labor analgesic in this country.

Tramadol hydrochloride a synthetic analogue of codeine has been suggested as equally effective analgesic and is cheaper than meperidine. It may be preferred over meperidine as it is associated with less sedation.[3] Since reservations are expressed about maternal[4] and neonatal effects due to placental permeability of 100 mg of tramadol administration by some authors,[56] we decided to study the effect of 50 mg of tramadol in comparison with 100 mg tramadol and evaluated with 75 mg meperidine injections. Since it is reported that administration of meperidine in the deltoid is likely to produce better analgesic effect by reaching mean peak levels earlier than when given at gluteal region,[7] to avoid discrimination the injection was given at deltoid region for all the three intervention groups. Emetic side effects of the opioid drugs are well established and to overcome it promethazine was added to all the groups. Despite combination of the antiemetic with analgesic, 7-11% of women had nausea and vomiting. The combination has not shown to reduce the incidence and severity of side effects.[8]

The case characteristics of age and weight were similar and so were the fetal/neonatal weights. Although labor with occiput-posterior position is said to be associated with longer duration and more painful labor, we did not note down fetal head position at recruitment. It may not be an influencing variable since it would change during the course of labor in most of them. Both the tramadol groups showed lesser maternal and neonatal effects than the meperidine group, but women receiving 50 mg tramadol recorded less pain relief than the other groups (P < 0.05). Obtaining similar results, Veigas et al. (1993)[9] opined that tramadol 100 mg is as effective as pethidine 75 mg but has a superior safety profile.

Declaration: Results are part of the MD dissertation work submitted to Manipal University. The study was conducted at Kasturba Medical College and Hospital, Manipal.