Obstetrical analgesia with tramadol ?

 

Joseph Eldor, MD

 

csen_international@csen.com

 

 

Bitsch et al. (1) used in 1980 parenteral analgesia with Tramal in 23 normal deliveries. The results were compared with a group of normal deliveries in which analgesia was achieved with pethidine. Both medications exerted an identical analgetic efficiency. No adverse side effects were observed with Tramal concerning the follow-up of labour or the newborn.

 

Long and Yue (2) evaluated the safety and analgesic efficacy of patient controlled intravenous analgesia (PCIA) with tramadol, and compared its benefits and risks with combined spinal-epidural analgesia (CSEA)+ patient controlled epidural analgesia (PCEA). Eighty American Society of Anesthesiologist (ASA) I-II at term parturients in active labor were randomly divided into 3 groups: the control group (n = 30) received no analgesia; group A (n = 30) received spinal administration with ropivacaine 2.5 mg and fentanyl 5 microg, then with PCEA; group B (n = 20) received 1 mg/kg tramadol loading dose i.v. PCIA with 0.75% tramadol and it included: PCA dose 2 ml, lockout time 10 minutes, background infusion 2 ml/h, total dose no more than 400 mg. The intensity of pain was evaluated using Visual Analogue Scale (VAS). Both group A and B showed good pain relief. VAS pain scores were significantly decreased in group A and B compared with those in the control group (P < 0.01). In comparison with group B, the VAS pain scores decreased in group A (P < 0.05). The onset times of analgesia in group A were shorter than those in group B (P < 0.05). Apgar scores in group B were lower than those in group A (P < 0.05). The periods of second stage of labor in group A were longer than those in the control group and group B (P < 0.05). The cesarean delivery rate was significantly higher in the control group (16.7%) than in group A (3.3%) and group B (5.0%), but it did not differ between group A and B. There were no significant differences in vital signs, fetal heart rate, degree of motor block, and uterine contractions among the 3 groups. PCIA with tramadol is now a useful alternative when patients are not candidates for CSEA for labor, or do not want to have a neuraxial block anesthesia. However, sometimes it may not provide satisfactory analgesic effect.

 

Jain et al. (3) compared analgesic efficacy of intramuscular opioids: meperidine and tramadol with epidural analgesia. One hundred and twenty-eight term nulliparous women with singleton pregnancy and vertex presentation were randomized to receive either epidural (n=43), meperidine (n=39) or tramadol (n=44). A visual analog scale (VAS) was used to assess the severity of pain. The parameters analyzed were analgesic efficacy, effect on labor, other maternal side effects, perinatal outcome and maternal satisfaction. Median VAS scores following first dose were 0 (0-5), 5 (3-8) and 5 (3-8) in epidural, meperidine and tramadol groups, respectively. Ninety percent of women rated analgesia as good to excellent in the epidural group as compared with 72% of women in the meperidine group and 65% in tramadol group. However, epidural caused a significant prolongation of first (P<0.05) and second (P<0.01) stage of labor with an increased number of operative deliveries (27% in the epidural, 7.6% in the meperidine, and 11.4% in the tramadol groups, P<0.05). In the epidural group 40% women had urinary retention and 16% had motor weakness, whereas sedation was the only side effect seen in the meperidine (41%) and tramadol groups (9%). Respiratory depression was noted among three neonates in the meperidine group, two in the tramadol group and none in the epidural group. The analgesic efficacy and maternal satisfaction is better with epidural analgesia than with opioids. Analgesia provided by meperidine and tramadol is comparable and approximately 50% of women rated the analgesia as good. Meperidine is better in the second stage than tramadol. Hence in developing nations where availability of facilities is the main limiting factor, intramuscular opioids can be considered suitable alternatives.

 

Keskin et al. (4) evaluated and compared the analgesic efficacy and adverse effects of tramadol and pethidine in labor. Fifty-nine full term parturients were randomly assigned to one of two groups in active labor. Group 1 received 100 mg pethidine; group 2, 100 mg tramadol, intramuscularly. Analgesic efficacy, maternal side effects, changes in the blood pressure, heart rate, and duration of labor were assessed. At 30 and 60 min after drug administration, pain relief was greater in the pethidine group than in tramadol group. The incidence of nausea and fatigue was higher in the tramadol group. Following drug administration the decrease in systolic and diastolic blood pressure and the increase in heart rate were statistically significant in both groups. No significant difference was found between the groups when compared for duration of labor and Apgar scores. None of the neonates developed respiratory depression. Pethidine seems to be a better alternative than tramadol in obstetric analgesia because of its superiority in analgesic efficacy and low incidence of maternal side effects.

 

The need for analgesia to overcome pain in labour is highly requested by women today. Various ways either non pharmachologic e.g. Emotional sustain, psycho-prophylactic preparation, yoga and hypnosis or pharmachologic such as epidural blockade or parenteral are used. Therefore in Fieni et al. (5) evaluated the efficacy and tolerability of the two opioids usually used today in parenteral analgesia to reduce pain during labour: Tramadol and Meperidine. They studied two groups of patients each made up of 20 women in labour, all at term and with a physiologic course of pregnancy. 75 mg i.m. of Meperidine were administered in the first group while in the second group 100 mg i.m. of tramadol were administered. Various maternal, fetal and neonatal parameters were then monitored demonstrating--A moderate maternal analgesic effect in both drugs (evaluated through the analogic grading of pain). In the group to whom Meperidine was given, sedative effects on the mother were observed associated with respiratory depression in the newborn (the latter evaluated through the Apgar index at 1st and 5th minute of life and pH of the blood obtained at the umbilical cord). Tramadol gave an analogous analgesic effect, with better tolerability for the absence of collateral effects on the mother, fetus and newborn.

 

The pharmacology, pharmacokinetics, efficacy, adverse effects, and dosage and administration of tramadol were reviewed (6). Tramadol is a synthetic analogue of codeine that binds to mu opiate receptors and inhibits norepinephrine and serotonin reuptake. It is rapidly and extensively absorbed after oral doses and is metabolized in the liver. Analgesia begins within one hour and starts to peak in two hours. In patients with moderate postoperative pain, i.v. or i.m. tramadol is roughly equal in efficacy to meperidine or morphine; for severe acute pain, tramadol is less effective than morphine. Oral tramadol can also be effective after certain types of surgery. Tramadol and meperidine are equally effective in postoperative patient-controlled analgesia. In epidural administration for pain after abdominal surgery, tramadol is more effective than bupivacaine but less effective than morphine. In patients with ureteral calculi, both dipyrone and butylscopolamine are more effective than tramadol. For labor pain, i.m. tramadol works as well as meperidine and is less likely to cause neonatal respiratory depression. Oral tramadol is as effective as codeine for acute dental pain. In several types of severe or refractory cancer pain, tramadol is effective, but less so than morphine; for other types of chronic pain, such as low-back pain, oral tramadol works as well as acetaminophen-codeine. Common adverse effects of tramadol include dizziness, nausea, dry mouth, and sedation. The abuse potential seems low. The recommended oral dosage is 50-100 mg every four to six hours. Tramadol is an effective, if expensive, alternative to other analgesics in some clinical situations.

 

Tramadol is a cyclohexanol derivative with mu-agonist activity. It has been used as an analgesic for postoperative or chronic pain since the late 1970s, and became one of the most popular analgesics of its class in Germany. International interest has been renewed during the past few years, when it was discovered that tramadol not only acts on opioid receptors, but also inhibits serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (norepinephrine) reuptake. Radbruch et al. (7) reviewed the risk-benefit assessment of tramadol in the management of acute and chronic pain syndromes. Tramadol has been used intraoperatively as part of balanced anesthesia. Such use is under discussion, however, as it was associated with a high incidence of intraoperative recall and dreaming, and postoperative respiratory depression has been described after intraoperative administration of high doses. Postoperatively, intravenous and intramuscular tramadol has been used with good efficacy. Analgesic doses were comparable with pethidine (meperidine) and 10 times higher than morphine. Nausea and vomiting were the most frequently reported adverse effects. In controlled studies, hemodynamic and respiratory parameters were only minimally impaired. The risk of severe respiratory depression in typical dosages is negligible in comparison with other opioids used for postoperative pain management. Tramadol has been used with good results for the management of labour pain without respiratory depression of the neonate. It was also effective for the treatment of pain from myocardial ischemia, ureteric colic and acute trauma. Good results have been published for cancer pain management with tramadol in several studies. The potential for abuse or addiction seems to be minimal, and serious complications have not been reported. For patients with severe pain, the efficacy of morphine is superior, and most patients with adequate analgesia from tramadol had to be changed to a more potent opioid after a few weeks due to increased nociceptive input during tumor progression. Tramadol can be recommended as a safe and efficient drug for step II according to the World Health Organization guidelines for cancer pain management.

 

Ninety primigravide were randomly allocated into three groups at the beginning of active phase of labor (8). Dihydroetorphine hydrochloride (DHE) was administered to group A (n = 30), tramadol to group B (n = 30), and group C (n = 30) was a blank control. Various parameters about analgesia effects, progress of labour and fetal and neonatal well-being were investigated and also umbilical artery and vein blood gases analyzing were carried out in all cases. As a result, the effective rate of pain relief in group A was 67% and in group B 63% (P > 0.05). The average time of onset of action in DHE group was 16.5 +/- 2.9 minutes which was significantly shorter than 26.1 +/- 5.4 minutes in tramadol group (P = 0.0001). There were higher rate (36.7%) of operative intervention (forceps and vaginally or cesarean section) and a higher average amount of postpartum hemorrhage in group A, as compared with the control group, but no significant difference was shown between group B and group C. No difference was found in other parameters (among the three groups - duration of labour, Apgar scores of neonates, cord blood gases, etc.). The conclusion is that, both DHE and tramadol may have a good effect on pain relief in labour. The time of onset of action in DHE group is significantly shorter than that in tramadol group. Neither analgesics cause circulation and respiratory depression in the mother and neonates, but DHE may have influence on uterine contraction.

 

Lehmann (9) reviewed the use of tramadol in the management of acute pain. Tramadol is a weak opioid analgesic with a potency comparable to that of pethidine. While it is not recommended as a supplement to general anesthesia because of its insufficient sedative activity, tramadol has been successful in the treatment of postoperative pain. Several studies have demonstrated its analgesic efficacy after intramuscular and intravenous application, both in adults and children. Moreover, negligible respiratory depressant activity and only minor side effects have consistently been shown. Patient-controlled analgesia with tramadol has been frequently employed and was well accepted by the patients. There have been only a few studies of oral or spinal application of tramadol in acute pain states. Tramadol has also been used for the control of pain associated with labour and acute myocardial infarction, as well as for the management of trauma pain. In summary, tramadol can be recommended as a basic analgesic for the treatment of patients with moderate to severe pain.

 

The analgesic efficacy and safety of tramadol 50 mg, 100 mg and pethidine 75 mg, administered intramuscularly were compared in a randomized, double-blind clinical trial in 90 pregnant women with labour pain (10). Pain relief was measured by a 4-point verbal rating scale 10, 20, 30, 45 and 60 min after the administration of study drugs. The average total pain relief score within the first hour was 0.9 with tramadol 50 mg, 1.7 with tramadol 100 mg and 1.7 with pethidine 75 mg. In comparison to both tramadol doses the administration of pethidine was associated with a significantly higher frequency of adverse events and a significantly lower respiratory rate in the neonates. The results indicate that tramadol 100 mg is as effective as pethidine 75 mg but has a superior safety profile.

 

Kainz et al. (11) examined in a prospective, randomised, blind study the analgesic potency and tolerance of intramuscular Tramadol compared to a standard obstetric analgesia with Pethidine. Triflupromazine was administrated in combination with the two tested analgesics in order to study its efficacy in alleviating the emetic side effects of the tested analgesics. 66 parturients were randomly assigned to three groups: group A: 100 mg Tramadol (Tramal), group B: 100 mg Tramadol (Tramal) and 10 mg Triflupromazine (Psyquil), group C: 50 mg Pethidine (Alodan) and 10 mg Triflupromazine (Psyquil). No significant differences concerning duration of labour, FHR-alterations, umbilical cord blood gases, respiration pattern and Apgar Scores of the neonate occurred. In all three groups the analgesic effect was equally good. Combination of the analgesic with the antiemetic showed no reduction of the incidence and severity of side effects.

 

Because tramadol does not exhibit a depressive effect on ventilatory activity it is often be used in the obstetrical analgesia, at most in the form of an intramuscular injection. In a prospective study on 49 women under labour the clinical effect of the noninvasive rectal application of Tramadol, Pethidin, and Denaverin has been compared (12). The first dosage was 100 mg of all substances. Around half of the women said that analgetic effect was good or very good. The effect was the same in all treatment groups. Because of a low incidence of maternal side effects, the absence of side effects on the newborn, and near the same results on the analgetic effect of parenteral application in other studies, tramadol suppositories can be recommended for obstetrical analgesia.

 

Morphine derivatives are the most frequently used analgetic substances in obstetrics today. Nevertheless, nausea, vomiting, weariness, and somnolence are common side effects of these drugs. Moreover opiates exhibit a depressive effect on ventilatory activity. As many studies have demonstrated tramadol does not show a depressive effect to such a high degree. Husslein et al. (13) in a prospective randomized trial compared the efficacy as well as the safety of 100 mg tramadol and 100 mg pethidine in 40 women asking for pain relief during labour. The duration of labour was slightly but not statistical significantly shorter in the pethidine group. An analgetic effect could be observed in the pethidine as well as the tramadol group by both the pregnant women and the attending physician about 10 min after application lasting for about 2 hours. Concerning the side effects tramadol highly contrasted with pethidine. There were less cases of weariness and somnolence and the ventilatory frequency of the newborn babies tended to be higher than in the pethidine group. The serum levels of tramadol in umbilical and maternal veins demonstrated values of 0.83 +/- 0.15 (mean +/- SEM; quotient). The results of this study seem to establish an analgetic effect of tramadol similar to pethidine but with less side effects.

 

Bibliography

 


1. Bitsch M, Emmrich J, Hary J, Lippach G, Rindt W.
Obstetrical analgesia with tramadol. Fortschr Med. 1980 Apr 24;98(16):632-4.

2. Long J, Yue Y. Patient controlled intravenous analgesia with tramadol for labor pain relief. Chin Med J (Engl). 2003 Nov;116(11):1752-5.
3. Jain S, Arya VK, Gopalan S, Jain V.
Analgesic efficacy of intramuscular opioids versus epidural analgesia in labor. Int J Gynaecol Obstet. 2003 Oct;83(1):19-27.
4. Keskin HL, Keskin EA, Avsar AF, Tabuk M, Caglar GS.
Pethidine versus tramadol for pain relief during labor. Int J Gynaecol Obstet. 2003 Jul;82(1):11-6.
5. Fieni S, Angeri F,
Kaihura CT, Ricci L, Bedocchi L, Galanti B, Rossi T, Benassi G, Benassi L. Evaluation of the peripartum effects of 2 analgesics: meperidine and tramadol, used in labor. Acta Biomed Ateneo Parmense. 2000;71 Suppl 1:397-400.
6. Lewis KS, Han NH.
Tramadol: a new centrally acting analgesic. Am J Health Syst Pharm. 1997 Mar 15;54(6):643-52.
7. Radbruch L, Grond S, Lehmann KA.
A risk-benefit assessment of tramadol in the management of pain. Drug Saf. 1996 Jul;15(1):8-29.
8. Li E, Weng L.
Influence of dihydroetorphine hydrochloride and tramadol on labor pain and umbilical blood gas. Zhonghua Fu Chan Ke Za Zhi. 1995 Jun;30(6):345-8.
9. Lehmann KA.
Tramadol for the management of acute pain. Drugs. 1994;47 Suppl 1:19-32.
10. Viegas OA, Khaw B, Ratnam SS.
Tramadol in labour pain in primiparous patients. A prospective comparative clinical trial. Eur J Obstet Gynecol Reprod Biol. 1993 May;49(3):131-5.
11. Kainz C, Joura E, Obwegeser R, Plockinger B, Gruber W.
Effectiveness and tolerance of tramadol with or without an antiemetic and pethidine in obstetric analgesia. Geburtshilfe Perinatol. 1992 Mar-Apr;196(2):78-82.
12. Bredow V.
Use of tramadol versus pethidine versus denaverine suppositories in labor--a contribution to noninvasive therapy of labor pain. Zentralbl Gynakol. 1992;114(11):551-4.
13. Husslein P, Kubista E, Egarter C.
Obstetrical analgesia with tramadol--results of a prospective randomized comparative study with pethidine. Z Geburtshilfe Perinatol. 1987 Nov-Dec;191(6):234-7.