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Tramadol versus Pethidine for Labour Analgesia By Abeer A.M.Hassanin* and Ameer A. Abdullah ** Departments of *Anesthesia & **Obstetrics and Gynecology, El-Minia Faculty of Medicine Correspondance: Department of Obstetrics & Gynaecology, Minia University, Minia, Egypt, 61111; e-mail: [email protected].

ABSTRACT: Background: Labour pain is among the most sever pain experienced by women. Mostly all women request analgesia to overcome this pain. In our hospital we usually use epidural, spinal analgesia or intramuscular administration pethidine (50 mg is the standard dose of pethidine used in our hospital) for women that refuse neuroaxial blocks. But there was high incidence of nausea and vomiting and drowsiness with the use of pethidine. There are many studies that studied the use of tramadol in labour analgesia and recommended its use as it has less maternal side effect. So we decided to do this study to clarify if intramuscular administration of tramadol is better than intramuscular administration of pethidine with respect to: analgesic efficacy, duration of labour and side effects in labour. Methods: One hundred and twenty full-terms parturient in active labour were randomly allocated to two equal groups. Pethidine group received 50 mg pethidine intramuscularly and tramadol group received 100 mg tramadol intramuscularly. The analgesic efficacy, duration of the labour, maternal side-effects, mode of delivery and Apgar score were assessed. Results: Women in pethidine group had lower visual analog pain scores (VAPS) all over the time of the study but it was non significant statistically. There was no significant difference as regard the duration of labour for first stage (183.5 vs. 178.08 min; and for second stage (29.37 vs. 27.73 min). There was a significantly higher incidence of nausea and vomiting (21 (35%) in tramadol group vs. 12 (20%) women) in pethidine group. And there was a significantly higher incidence of drowsiness (36 (60%) in pethidine group vs. 22 (36.7%) women) in tramadol group. Conclusion: Both 100 mg tramadol and 50 mg pethidine provide moderate analgesia in labour. Tramadol seems to cause lower incidence of drowsiness, but it cause higher incidence of nausea and vomiting. So intramuscular administration of tramadol was not better than intramuscular administration of pethidine with respect to: analgesic efficacy, duration of labour and side effects in labour. KEYWORDS: Labour analgesia

Pethidine

Tramadol

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INTRODUCTION: There are many methods of analgesia during labour, which are broadly classified into regional and nonregional techniques with the nonregional being further classified as pharmacological and non-pharmacological methods. Studies in New Zealand and the United Kingdom have found that more than 95% of hospitals surveyed routinely offered intramuscular pethidine1, 2. Most women who deliver in modern obstetric units request some form of pharmacological and non3 pharmacological pain relief . The ideal obstetric analgesic should provide potent analgesic efficacy with minimal maternal and neonatal adverse effects. Epidural analgesia is the most effective way of relieving pain in labour, providing complete relief in 95% of cases. It also has the benefit of avoiding need for greater analgesia, general anesthetic if vacuum extraction or Cesarean section is required4. But, some women does not wish to have an epidural analgesia so administration of injectable opioids such as pethidine is a simple and less invasive alternative5. Parenteral opioids are part of standard care during labour in many obstetric units. A Cochrane review assessed the effectiveness, safety and acceptability to women of different types, doses and modes of adminis-tration of Parenteral opioid analgesia during labour stated that parenteral opioids provide some relief from pain in labour but are associated with adverse effects6. Pethidine is one of the most frequently used opiate agonists that exerts its effects through opioid receptors. It can be administered orally or parenterally. When used intra-muscularly, its analgesic effect starts within 10–20 min, and its duration of effect is shorter than that of morphine and lasts 2–4 h6.

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 depression7. Tramadol is a centrally acting analgesic that displays its effects by modifying transmission of pain impulses by altering monoamine reuptake mechanisms. It can be administered orally, rectally, intravenously or intramuscularly, and it is principally metabolized in the liver and 90% of it is excreted with urine8. Main side-effects of pethidine and tramadol are observed in the central nervous system (dizziness, drowsiness, fatigue, headache, and sedation), gastrointestinal system (nausea, vomiting, and constipation), cardiovascular system (orthostatic hypotension) and respiratory depression7. Tramadol crosses the placenta, but appears safe in labour9. Its intravenous administration causes far less respiratory depression than pethidine10. The aim of this study was to clarify if intramuscular administration of tramadol is better than intramuscular administration of pethidine with respect to: analgesic efficacy, duration of labour and side effects in labour. Materials and methods: After approval of the local ethical committee of El-Minia univer-sity hospital and obtaining written informed consent, one hundred twenty full-terms parturient from March 2010 to March 2011, who were admitted to the labour ward of obstetrics in ElMinia university hospital, were assessed for randomization in our randomized prospective double blind study. Neither the observer nor the patient knows the study group allocation.

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and second stage and hemodynamic We included: 120 women with fullterm variables. Maternal hypotension was vertex presentation in active labour defined as a decrease in systolic blood (that was defined as the presence of at pressure below 20% of baseline least three regular, painful uterine recordings. Respiratory depression was contractions over 10 min with cervical defined as respiratory rate below 8. dilatation 4 cm), women who desired Common side-effects as drowsiness, labour analgesia and refused nausea and vomiting were recorded neuroaxial analgesia and who had a and compared. pain score of ≥ 4 by VAPS. Follow up of VAPS was done by Women were excluded if cervical anesthesiologist (who was blinded with dilatation of ≥ 5 cm, if they had the study groups) every 30 min until obstetric complication or any evidence delivery (0 representing no pain and 10 of cephalopelvic disproportion. as the worst pain). Women were randomly allocated into Apgar scores were recorded at one and two groups. Rando-mization was based five minutes by neonatologist. Who on computer-generated numbers. was blind to the study group allocation. Women in the first group (60 cases) received intra-muscular 50 mg Statistical Analysis: Results are expressed as pethidine and women in the second mean ± standard deviation (SD) or group (60 cases) received numbers and percentage. All data were intramuscular 100 mg tramadol. After analyzed using SPSS 10.0 package four hours of the drug injection, the (SPSS Inc., Chicago, IL, USA). same dose can be repeated on demand. Quantitative analysis was done using For prevention of newborn respiratory Student's t-test. For qualitative analysis depression, we withheld pethidine once chi-square test was used. Nonthe labour had progressed to 8 cm parametric data were compared with cervical dilatation as it was Mann–Whitney U-test. A P-value less recommended by Jain et al.,11 but than 0.05 were considered significant. tramadol was not withheld in the A sample size of 56 patients per group second stage of labour. The drugs were was determined to be adequate to prepared and administrated by the demonstrate a mean difference of 13 attending nurse. mm in VAPS with power of 90%. Follow up of the progress of labour was done by the attending obstetrician Results: There was no significant difference who was blinded to the treatment between the two groups as regard age, groups. height, weight, period of gestation, We recorded the duration of first stage fetal weight, and cervical dilatation and second stage, fetal heart rate, mode before analgesia (Table 1). of delivery, any complication of first Table (1): Maternal characteristics Pethidine Tramadol P-value N = 60 N = 60 Characteristics 29.63 ± 7.12 28.37 ± 6.85 0.325 Maternal age (years) 162.7 ± 5.4 160.9 ± 7.9 0.147 Height (cm) 73.2 ± 13.5 71.2 ± 15.7 0.455 Weight (kg) 39.1 ± 01.7 38.9 ± 1.5 0.495 Gestational age (weeks) 3238 ± 525.6 3342 ± 475.1 0.257 Fetal weight (g) 3.7 ± 0.7 3.9 ± 0.6 0.095 Cervical dilatation before analgesia (cm)

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There was no significant difference between the two groups in VAPS all over the time of the study. Women in pethidine group had lower VAPS all over the time of the study but it was non significant statistically (Table 2). Table (2): Pain scores Pain score Pethidine Tramadol P-value N = 60 N = 60 9 ± 0.45 8.89 ± 0.5 0.207 Before 6.5 ± 0.7 6.6 ± 0.82 0.473 30 min 6.7 ± 0.98 6.9 ± 0.69 0.198 60 min 6.9 ± 0.92 7.2 ± 1.54 0.197 90 min 7.2 ± 1.78 7.8 ± 1.65 0.057 120 min 7.5 ± 1.22 7.9 ± 1.87 0.167 150 min 7.9 ± 1.68 8.1 ± 0.89 0.416 Stage 2 There was no significant difference between the two groups as regard the duration of labour for first stage and also for second stage (Table 3). Table (3): Duration of labour Pethidine Tramadol N = 60 N = 60 Duration of stage P-value 0.521 Duration of active first stage (min) 183.5 ± 58.75 178.08 ± 28.3 29.37 ± 21.85 27.73 ± 25.9 0.708 Duration of second stage (min) Details of other labour characteristics in the two groups are summarized in (Table 4). Table (4): Labour characteristics. Pethidine Tramadol Characteristic N = 60 N = 60 P-value 54 (90%) 57 (95%) 0.149 Normal vaginal delivery 2 (3.33%) 0 (0%) 0.077 Operative vaginal delivery 4 (6.66%) 3 (5%) 0.349 Cesarean section 2 (3.33%) 1 (1.66%) 0.278 Acute fetal distress 2 (3.33%) 1 (1.66%) 0.278 Thick meconium-stained amniotic fluid There was a significantly higher incidence of nausea and vomiting (21 (35%) in tramadol group vs. 12 (20%) women) in pethidine group. And there was a significantly higher incidence of drowsiness (36 (60%) in pethidine group vs. 22 (36.7%) women) in tramadol group (Table 5).

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Table (5): Maternal side effects.

Nausea and vomiting Drowsiness

Pethidine N = 60 12 (20%) 36 (60%)

Tramadol N = 60 21 (35%) 22 (36.7%)

P-value 0.0329 0.0005

All neonates had an Apgar score above 7 at one and five minutes. DISCUSSION: In our study both 100 mg tramadol and 50 mg pethidine can provide moderate analgesia in labour. Women in pethidine group had lower VAPS all over the time of the study but it was non significant statistically. In agreement with our study Fieni et al and Viegas et al showed that 100 mg tramadol was effective as 75 mg pethidine in pain relief in labour9,12. But the study that was done by keskin et al who studied 59 full term parturient into 2 groups the first group received 100 mg pethidine and the second group received 100 mg tramadol showed that 100 mg pethidine was more effective in pain relief at 30 and 60 min when compared to 100 mg tramadol and also the incidence of nausea was higher in tramadol group and they concluded that pethidine seems to be better than tramadol in obstetric analgesia as it was superior in analgesic efficacy and low maternal side effects13. In our study there was a significantly higher incidence of nausea and vomiting in tramadol group vs. pethidine group. And there was a significantly higher incidence of drowsiness in pethidine group vs. tramadol group. 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 group9,12. Despite administration of lower doses of pethidine, the results of our study are similar to these studies as

regard drowsiness, but tramadol cause signifi-cantly higher incidence of nausea and vomiting than pethidine. Long and Yue revealed that tramadol is a useful drug for labour analgesia, with low incidence of side-effects on the mother, fetus and new born14. The was no significant difference between the two groups as regard mean duration of labour in our study. In agreement with our result there was no difference between tramadol and pethidine with respect to the effects on the duration of labor12. Also in the study that was done by Keskin et al the mean duration of labor was approximately 2 h in both groups, they used 100 mg pethidine and 100 mg tramadol, no statistical difference in the duration of labour was found between pethidine group (126 min) and tramadol group (115 min)13. In Husslein's study the duration of labour was slightly but not statistical significantly shorter in the pethidine group15. In our study most of the patients delivered within four hours of analgesic administration. In a study by Viegas et al., the mean duration of labour was 7.9 h after administration of 100 mg i.m. tramadol and 7.8 h after administration of 75 mg i.m. pethidine12. In the study that was done by Khooshideh and Shahriari, they found that both 100 mg tramadol and 50 mg pethidine provide moderate analgesia in first stage of labour. Tramadol cause a shorter duration of labour and lower incidence of maternal side-effects16.

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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 use17, but numerous studies have reported that Apgar scores are not altered, and respiratory depression requiring resuscitation is not observed with pethidine and tramadol18. 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 on the newborns. However, all of the patients in this study received only one dose of tramadol or pethidine, because all of the patients in the two groups delivered within four hours after administration of first dose. In conclusion, this study showed that tramadol 100 mg caused a lower incidence of drowsiness and higher incidence of nausea and vomiting than 50 mg pethidine. However, both 100 mg tramadol and 50 mg pethidine can provide moderate analgesia in labour. Women in pethidine group had lower VAPS all over the time of the study but it was non significant statistically. So tramadol was not better than pethidine as regard labour analgesia, duration of labour and side effects in labour. References: 1. Lee K, Ho KM, Obstetrics regional analgesia services in New Zealand: a national survey. New Zealand Medical Journal 2004: 117: U177. 2. Saravanakumar K, Garstang JS, Hasan K. Intravenous patient controlled analgesia for labour: a survey of UK Practice. International Journal of Obstetric Anesthesia 2007; 16: 221– 225.

3. Thurlow JA, Laxton CH, Dick A, Waterhouse P, Sherman L, Goodman NM. Remifentanil by patientcontrolled analgesia compared with intramuscular meperidine for pain relief in labor. Br J Anesth 2002; 88: 347–348. 4. Sartore A, Pregazzi R, Bortoli P, et al. Effects of epidural analgesia during labor on pelvic floor function after vaginal delivery. Acta Obstetric Gynecology Scand. 2003;82 (2):143-6. 5. Bricker L, Lavender T. Parenteral opioids for labor pain relief: A systematic review. Am J Obstetric Gynecology 2002; 186: 94–109. 6. Ullman R, Smith LA, Burns E, Mori R, Dowswell T. Parenteral opioids for maternal pain relief in labour. Cochrane Database of Systematic Reviews 2010; (9). 7. Claahsen-van der Grinten HL, Verbruggen I, Van den Berg PP, Sporken JM, Kollee LA. Different pharmacokinetics of tramadol in mothers treated for labour pain and in their neonates. Eur J Clin Pharmacol 2005; 61: 523–529. 8. Lee CR, McTavish D, Sorkin EM. Tramadol. A preliminary review of its pharmacodynamic and pharmacokinetic and therapeutic potential in acute and chronic pain states. Drugs 1993; 46(2):313 –340. 9. Fieni S, Angeri F, Kaihura CT et al. Evaluation of the peripartum effects of 2 analgesics: Meperidine and tramadol, used in labor. Acta Biomed Ateneo Parmense 2000; 71: 397–400. 10. Claahsen-van der Grinten HL, Verbruggen I, Van den Berg PP, Sporken JM, Kollee LA. Different pharmacokinetics of tramadol in mothers treated for labour pain and in their neonates. Eur J Clin Pharmacol 2005; 61: 523–529. 11. Jain S, Arya VK, Gopalan S, Jain V. Analgesic efficacy of intramuscular opioids versus epidural analgesia in

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labor. Int J Gynecol Obstet 2003; 83: 19–27. 12. Viegas OA, Khaw B, Ratnam SS. Tramadol in labor pain in primi-parous patients. A prospective compa-rative clinical trial. Eur J Obstet Gynecol Reprod Biol 1993; 49: 131–135. 13. 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: 11–16. 14. Long J, Yue Y. Patient controlled intravenous analgesia with tramadol for labor pain relief. Chin Med J 2003; 116: 1752–1755. 15. Husslein P, Kubista E, Egarter C. Obstetrical analgesia with tramadol – Results of a prospective randomized

comparative study with pethidine. Z Geburtshilfe Perinatol 1987; 191: 2. 16. Khooshideh M, Shahriari A. A comparison of tramadol and pethidine analgesia on the duration of labour: a randomized clinical trial. Aust N Z J Obstet Gynaecol. 2009; 49(1):59-63. 17. Tsui MH, Ngan Kee WD, Ng FF, Lau TK. A double blinded randomised placebo-controlled study of intramuscular pethidine for pain relief in the first stage of labour. Br J Obstet Gynaecol 2004; 111: 648–655. 18. Elbourne D, Wiseman RA. Types of intra-muscular opioids for maternal pain relief in labour. Cochrane Database Systematic Reviews 2006; (3).