A comparison of tramadol and pethidine analgesia on the duration of labour: A randomised clinical trial

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1 Australian and New Zealand Journal of Obstetrics and Gynaecology 2009; 49: DOI: /j X x Blackwell Publishing Asia Original Article A comparison of tramadol and pethidine analgesia on the duration of labour: A randomised clinical trial Maryam KHOOSHIDEH 1 and Ali SHAHRIARI 2 1 Department of Obstetrics and Gynaecology, and 2 Department of Anaesthesiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran Background: The ideal obstetric analgesia should provide analgesic efficacy without attenuation of uterine contractions. Aims: To compare the outcome of intramuscular administration of pethidine and tramadol in labour analgesia. Methods: One hundred and sixty full-term parturients were randomly assigned to two equal groups in active labour. Group P received 50 mg pethidine; and group T, 100 mg tramadol intramuscularly. Primary outcome measure was the duration of the labour. The analgesic efficacy, maternal side-effects, mode of delivery, maternal satisfaction and Apgar score as the secondary outcome were assessed. Results: The duration of labour was shorter in group T, for first stage (190 vs 140 min; P < ) and for second stage (33 vs 25 min; P = 0.001). There were no differences in Groups P and T with respect to median (7 vs 8) and maximum (7.5 vs 8) visual analog scores (VAS) for pain at 10 min and one hour after drug administration. Women in group P had lower VAS pain scores than those in group T in the second stage of labour (8 vs 9; P = 0/009). There was a significantly higher incidence of nausea and vomiting (35% vs 15%; P = 0.003) and drowsiness (80% vs 29%; P < ) in group P. Conclusion: Both 100 mg tramadol and 50 mg pethidine provide moderate analgesia in first stage of labour. Tramadol seems to cause a shorter duration of labour and lower incidence of maternal side-effects. However, its analgesic efficacy was not found to be as effective as pethidine, especially in the second stage of labour. Key words: duration of labour, pethidine, randomised trial, tramadol, VAS score. Introduction Adequate analgesia during labour has a positive influence on the course of labour. 1 Most women who deliver in modern obstetric units request some form of pharmacological and non-pharmacological pain relief. 2 The ideal obstetric analgesic should provide potent analgesic efficacy with minimal maternal and neonatal adverse effects. Epidural analgesia offers the best pain relief for many women in labour 1 but, where this is contraindicated or a woman does not wish to have an epidural analgesia, administration of injectable opioids such as pethidine is a simple and less invasive alternative. 3 6 Pethidine is one of the most frequently used opiate agonists. 1 Studies on pethidine have, however, consistently cast doubts on its effectiveness for maternal pain relief and raised concerns about its effects on the newborn. 6 In addition to the maternal sedating effects of pethidine, there is also the Correspondence: Dr Maryam Khooshiedeh, Department of Obstetrics and Gynaecology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran. alibenmahdi@yahoo.com Received 23 January 2008; accepted 10 August theoretical risk of maternal delayed gastric emptying, aspiration and respiratory depression. 7 Tramadol is a synthetic analog of codeine and a weak opioid agonist, and has been found to have analogous analgesic efficacy to pethidine but with a less sedative effect on the mother and less neonatal respiratory depression. 2,8 10 Main side-effects of both drugs are observed in the central nervous system (dizziness, drowsiness, fatigue, headache, sedation), gastrointestinal system (nausea, vomiting, constipation), cardiovascular system (orthostatic hypotension) and respiratory depression. 3 Tramadol crosses the placenta, but appears safe in labour. 5 Its intravenous administration causes far less respiratory depression than pethidine. 11 The aim of this study was to compare 100 mg tramadol and 50 mg pethidine intramuscularly (50 mg is the standard dose of pethidine used in this setting in our hospital in Iran) with respect to: duration of labour, analgesic efficacy and other side-effects in labour. Materials and methods Following Ethics approval and written informed consent, we recruited 160 full-term parturients during 2004, who were admitted to the labour ward of a tertiary referral centre for obstetrics in Zahedan, Iran, in this randomised prospective study. The inclusion criteria were as follow: 2009 The Authors 59 Journal compilation 2009 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists

2 M. Khooshideh and A. Shahriari Women aged between 18 and 40 years. Vertex presentation and expectancy for a non-complicated vaginal delivery. Uncomplicated singleton and term pregnancy in active labour (that was defined as the presence of at least three regular, painful uterine contractions over 10 min with cervical dilatation 4 cm). Patients who desired labour analgesia and who had a pain score of 5 by a 10-cm-long marked visual analog scale (VAS). Exclusion criteria were: cervical dilatation of 5cm, any evidence of cephalopelvic disproportion, uteroplacental insufficiency or presence of any medical/surgical complications. Also parturient with a history of alcohol or drug abuse and patients using monoamine-oxidase inhibitors, opioids and psychotropic drugs were excluded. All the women were randomly allocated into two groups. Randomisation was based on computer-generated codes kept in sequentially numbered opaque envelopes until just before use. This randomisation was operated by one of our colleague who is specialised in medical statistics. The patients in the first group (80 cases) received 50mg pethidine (group P) and the patients in the second group (80 cases) received 100 mg tramadol (group T), both of which were administrated intramuscularly. The same dose was repeated if subsequent demand was made after four hours of initial dose. Pethidine was withheld once the labour had progressed to 8 cm cervical dilatation as was recommended by Jain et al. 12 for prevention of new born respiratory depression, but tramadol was not withheld in the second stage of labour. The drugs were administrated by the attending obstetrician who was blinded to the treatment groups to the patients. Our primary study outcome was the duration of labour. Progress of labour was assessed by a partogram maintained for each woman by the attending obstetrician who was blinded to the treatment groups. Oxytocin, if required, was administered. Duration of first stage (from 4 cm cervical dilatation to full dilatation) and second stage, fetal heart rate, mode of delivery and any other complication of first and second stage were recorded and compared in the two groups. Also following analgesic administration, an anaesthesiologist who was blinded to the kind of treatment to each group, obtained the pain scores in order to evaluate analgesic efficacy at 10 and 30 min and one-h intervals until delivery following drug administration with 0 representing no pain and 10 as the worst pain. Homodynamic variables were recorded prior to the administration of analgesic and every 30 min following drug injection. The parturients were monitored with non-invasive blood pressure and pulse oximetry (SpO 2 ). Maternal hypotension was defined as a systolic blood pressure below 70 80% of baseline recordings and/or an absolute value below 100 mmhg and respiratory depression was defined as respiratory rate below 8. Common side-effects of analgesia as drowsiness, nausea and vomiting were recorded and compared. Neonatal evaluation was done by a neonatologist using Apgar scores at one and five minutes, and naloxone usage for any presumed opioid-induced respiratory depression and any other complications were also recorded. In addition, maternal satisfaction was assessed within 24 h after delivery by obstetrician who was blinded to the opioid injected using a five-point descriptive scale of excellent, very good, good, fair or poor. The desire to use the same analgesia in future was also enquired. On the basis of experience in duration of labour in pethidine treated parturient in a pilot investigation, it was assumed that a mean duration of ± would be observed. We assumed that a difference of 30 min in duration of labour would be clinically significant. Based on this assumption, 53 cases in each group will be enough to find such a difference by 80% power on a 5% significance (α =0.05, β =0.2). Results are expressed as mean ± standard deviation (SD). All data were analysed using SPSS 10.0 package (SPSS Inc., Chicago, IL, USA). Quantitative analysis was done using Student s t-test. For qualitative analysis chi-square test was used. Non-parametric data were compared with Mann Whitney U-test. A P-value less than 0.05 was considered significant. Results One hundred and sixty full-term parturients recruited and there were no withdrawals (Fig. 1). The two groups were comparable regarding age, parity, height, weight, period of gestation, fetal weight, cervical dilatation at initiation of analgesia and need for oxytocin use (Table 1). As seen in Table 2, the duration of labour was shorter in group T, for first stage (190 vs 140 min; P < ) and also for second stage (33 vs 25 min; P = 0.001) (Table 2). Table 1 Maternal characteristics (mean ± standard deviation) Characteristics Pethidine Tramadol Maternal age (years) ± ± 2.75 Height (cm) ± ± 6.8 Weight (kg) 70.1 ± ± 16 Gestational age (weeks) 39.0 ± ± 1.2 Fetal weight (g) 3228 ± ± Cervical dilatation at initiation of analgesia (cm) 3.6 ± ± 0.7 Systolic blood pressure before analgesia (mmhg) ± ± The Authors

3 Tramadol and pethidine in labour analgesia Figure 1 The flow of participants. Because all of the patients in group T delivered approximately within four hours after administration of first dose of tramadol, it was not required to administrate the next dose. In total, all of the patients in this study received only one dose of tramadol or pethidine. Details of other labour characteristics in the two groups are summarised in Table 3. At the beginning of active labour, all parturients felt severe pain and VAS pain scores were not significantly different within the groups. There were no differences in groups P and T with respect to median (7 vs 8) and maximum (7.5 vs 8) VAS for pain at 10 min and one hour after drug administration. Women in group P had lower VAS pain scores than those in group T in the second stage of labour (8 vs 9; P < 0.009) (Table 4). There was no difference in operative intervention (vacuum or caesarean section) rate, respiratory depression SpO 2 or hypotension between groups. There was a significantly higher incidence of nausea and vomiting (35% vs 15%; P = 0.003; relative risk (RR) = 1.61, 2009 The Authors 61

4 M. Khooshideh and A. Shahriari Table 2 Duration of labour in groups (mean ± standard deviation) Duration of stage Pethidine Tramadol P-value* Duration of active first stage (min) ± ± < Duration of second stage (min) ± ± ** Total duration of labour (min) ± ± < *P < 0.05 clinically significant. **With Mann Whitney U-test. Table 3 Labour characteristics (n %) Characteristic Pethidine N =80 Tramadol N =80 P-value* Relative risk (95% CI) Oxytocin used 28 (35) 26 (33) NS 1.06 ( ) Normal vaginal delivery 73 (91.25) 76 (95) NS 0.74 ( ) Operative vaginal delivery 2 (2.5) 0 (0) NS Not applicable Caesarean section 5 (6.25) 4 (5) NS 1.12 ( ) Indications for caesarean section Acute fetal distress 2 (2.5) 1 (1.25) NS 1.34 ( ) Thick meconium-stained amniotic fluid 2 (2.5) 1 (1.25) NS 1.34 ( ) Arrest of descent 1 (1.25) 2 (2.5) NS 0.66 ( ) Meconiun-stained amniotic fluid 6 (7.5) 4 (5) NS 1.22 ( ) Thin 4 (5) 3 (3.8) NS 1.15 ( ) Thick 2 (2.5) 1 (1.25) NS 1.34 ( ) *P < 0.05 clinically significant. Penthidine/tramadol. CI, confidence interval; NS, not significant. Table 4 Pain scores before and after analgesic administration at 10 min and 60 min and maximum pain scores during the first and second stage Pethidine Pain score Median Range Median Range P-value** Before NS 10 min NS 60 min NS Maximumscore over the stage NS Stage ** *P < 0.05 statistically significant **with Mann Whitney U-test. Using visual analog scale. Tramadol 95% confidence interval (CI): 1.21 to 2.15) and drowsiness (80% vs 29%; P < ; RR = 3.35, 95% CI: ) in group P compared with group T. All neonates (100%) had an Apgar score above 7 at one and five minutes. Analgesia provided by pethidine and tramadol is comparable and approximately 50% of women rated the analgesia as good to excellent. There were an almost equal percentage of women (35%) in groups P and T who expressed their dissatisfaction with analgesia and did not like to use it again. Discussion Intramuscular opioids have the advantage of ease of administration, are more economical, and can be an alternative for those women who are unwilling or unable to have epidural analgesia but want some form of pain relief. 12 The results of our study showed a remarkably shorter mean duration of labour in tramadol group. In Husslein s study the duration of labour was slightly but not statistical significantly shorter in the pethidine group. 13 In Keskin s study 1 in which 100 mg pethidine and 100 mg tramadol were used, no statistical difference in the duration of labour was found between pethidine group (126 min) and tramadol group (115 min). In our study most of the patients delivered within four hours of analgesic administration, and the duration of labour in only six patients in pethidine group was longer than four hours. In a study by Viegas et al., the mean duration of labour was 7.9 h after administration of 100 mg The Authors

5 Tramadol and pethidine in labour analgesia i.m. tramadol and 7.8 h after administration of 75 mg i.m. pethidine. 14 Also in a study by Frikha et al., in which 100 mg pethidine and 100 mg tramadol were used, ten of the 45 patients in pethidine group and nine of the 45 patients of the tramadol group delivered after four hours of analgesic administration. 15 The results of our study showing a remarkably shorter mean duration of labour is challenging. In a review by Elbourne and Wiseman, 16 trials were reviewed and they represented that there was no evidence of a difference between pethidine and tramadol in terms of interval to delivery, pain relief or operative delivery. 16 However, to compare the analgesic effects of the drugs seems to be difficult since the perception of pain or tolerance to pain varies among individuals. 12 The results of the present study indicated that although both pethidine and tramadol could not completely abolish labour pain, they produced comparable results in terms of maternal satisfaction with more than 50% of women rating analgesia as either good or excellent and that administration of 50 mg i.m. pethidine has an analgesic effect equivalent to that of 100 mg i.m. tramadol in pain relief in the first stage. However, pethidine seemed to be a better alternative than tramadol for analgesia in second stage of labour. Also, our study showed that there was a significant difference between pethidine and tramadol in the duration of labour. In some studies with 100 mg tramadol and 75 mg pethidine, the incidence of side-effects including nausea, vomiting and drowsiness has been found to be significantly higher in the pethidine group. 5,14,16 Despite administration of lower doses of pethidine, the results of our study are similar to these studies. Some studies have revealed that tramadol is a useful drug for labour analgesia, with low incidence of side-effects on the mother, fetus and new born. 14,17 Opioids especially pethidine have been implicated in causing neonatal respiratory depression. It has been postulated that this effect is mainly evident on intravenous administration of the drug and if the fetus is delivered within two to three hours following the drug use, 12 but numerous studies have reported that Apgar scores are not altered, and respiratory depression requiring resuscitation is not observed with pethidine and tramadol. 18,19 Our results support these previous data. This study has some limitations: we used 50 mg pethidine rather than 100 mg and it was withheld once 8 cm cervical dilatation was reached, for prevention of the respiratory depression effect of pethidine on the newborns. However, as we mentioned, all of the patients in this study received only one dose of tramadol or pethidine, because all of the patients in tramadol group delivered within four hours after administration of first dose of tramadol. In conclusion, this study showed that tramadol seems to cause a shorter duration of labour and a lower incidence of maternal side-effects. However, both 100 mg tramadol and 50 mg pethidine can provide moderate analgesia in first stage of labour. But the analgesic efficacy of tramadol was not found to be as good as pethidine especially in the second stage of labour. Further randomised investigations are needed to achieve an excellent pain relief by higher dosage of pethidine. References 1 Keskin HL, Aktepe Keskin E, Avsar AF, Tabuk M, Caglar GS. Pethidine versus tramadol for pain relief during labor. Int J Gynecol Obset 2003; 82: Thurlow JA, Laxton CH, Dick A, Waterhouse P, Sherman L, Goodman NM. Remifentanil by patient-controlled analgesia compared with intramuscular meperidine for pain relief in labor. Br J Anesth 2002; 88: Lee CR, McTavish D, Sorkin EM. Tramadol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in acute and chronic pain states. Drugs 1993; 46: Matheson I, Nylander G. Should meperidine still be administered to women in labor? 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