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      The maternal and neonatal effects of adding tramadol to 2% lidocaine in epidural anesthesia for cesarean section

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          Abstract

          Background:

          Opioid analgesics are commonly added to epidural local anesthetics to improve analgesia during surgery.

          Objectives:

          The goal of this study was to evaluate the maternal and neonatal effects of adding different doses of tramadol to 2% lidocaine in the epidural anesthesia for cesarean section.

          Patients and Methods:

          Ninety pregnant patients who were candidates for cesarean section under epidural anesthesia were randomly categorized into three groups. Group L received 2% lidocaine. In the LT50 and LT100 groups, 50 and 100 mg of tramadol were added to epidural 2% lidocaine. For additional analgesia during surgery, 2% lidocaine through epidural catheter or IV sufentanil were administered. Analgesia after surgery was provided by IV injection of meperidine. Onset and duration of sensory and motor blockades, total drug consumption, neonatal Apgar score, and complications were recorded.

          Results:

          In the LT100 group, onset of complete sensory and motor blockade at T6 was less than in the two other groups, but the highest level of sensory blockade and two segment regression and duration of motor blockades between the LT50 and LT100 groups were not significantly different, although they were higher and more prolonged than in the L group. Average lidocaine and sufentanil consumption during surgery between the LT50 and LT100 groups were not significantly different but were lower than in the L group. The incidence of maternal complications and neonatal Apgar scores were not significantly different between the three groups. In the LT50 and LT100 groups, the time until the first request for analgesics after surgery was prolonged, and average meperidine consumption was less than in the L group.

          Conclusions:

          The addition of tramadol to epidural 2% lidocaine offers advantages in cesarean section.

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          Most cited references24

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          Clinical pharmacology of tramadol.

          Tramadol, a centrally acting analgesic structurally related to codeine and morphine, consists of two enantiomers, both of which contribute to analgesic activity via different mechanisms. (+)-Tramadol and the metabolite (+)-O-desmethyl-tramadol (M1) are agonists of the mu opioid receptor. (+)-Tramadol inhibits serotonin reuptake and (-)-tramadol inhibits norepinephrine reuptake, enhancing inhibitory effects on pain transmission in the spinal cord. The complementary and synergistic actions of the two enantiomers improve the analgesic efficacy and tolerability profile of the racemate. Tramadol is available as drops, capsules and sustained-release formulations for oral use, suppositories for rectal use and solution for intramuscular, intravenous and subcutaneous injection. After oral administration, tramadol is rapidly and almost completely absorbed. Sustained-release tablets release the active ingredient over a period of 12 hours, reach peak concentrations after 4.9 hours and have a bioavailability of 87-95% compared with capsules. Tramadol is rapidly distributed in the body; plasma protein binding is about 20%. Tramadol is mainly metabolised by O- and N-demethylation and by conjugation reactions forming glucuronides and sulfates. Tramadol and its metabolites are mainly excreted via the kidneys. The mean elimination half-life is about 6 hours. The O-demethylation of tramadol to M1, the main analgesic effective metabolite, is catalysed by cytochrome P450 (CYP) 2D6, whereas N-demethylation to M2 is catalysed by CYP2B6 and CYP3A4. The wide variability in the pharmacokinetic properties of tramadol can partly be ascribed to CYP polymorphism. O- and N-demethylation of tramadol as well as renal elimination are stereoselective. Pharmacokinetic-pharmacodynamic characterisation of tramadol is difficult because of differences between tramadol concentrations in plasma and at the site of action, and because of pharmacodynamic interactions between the two enantiomers of tramadol and its active metabolites. The analgesic potency of tramadol is about 10% of that of morphine following parenteral administration. Tramadol provides postoperative pain relief comparable with that of pethidine, and the analgesic efficacy of tramadol can further be improved by combination with a non-opioid analgesic. Tramadol may prove particularly useful in patients with a risk of poor cardiopulmonary function, after surgery of the thorax or upper abdomen and when non-opioid analgesics are contraindicated. Tramadol is an effective and well tolerated agent to reduce pain resulting from trauma, renal or biliary colic and labour, and also for the management of chronic pain of malignant or nonmalignant origin, particularly neuropathic pain. Tramadol appears to produce less constipation and dependence than equianalgesic doses of strong opioids.
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            Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an 'atypical' opioid analgesic.

            Tramadol hydrochloride produced dose-related antinociception in mouse abdominal constriction [ED50 = 1.9 (1.2-2.6) mg/kg i.p.], hot-plate [48 degrees C, ED50 = 21.4 (18.4-25.3) mg/kg s.c.; 55 degrees C, ED50 = 33.1 (28.2-39.1) mg/kg s.c.] and tail-flick [ED50 = 22.8 (19.2-30.1) mg/kg s.c.] tests. Tramadol also displayed antinociceptive activity in the rat air-induced abdominal constriction [ED50 = 1.7 (0.7-3.2) mg/kg p.o.] and hot-plate [51 degrees C, ED50 = 19.5 (10.3-27.5) mg/kg i.p.] tests. The antinociceptive activity of tramadol in the mouse tail-flick test was completely antagonized by naloxone, suggesting an opioid mechanism of action. Consistent with this, tramadol bound with modest affinity to opioid mu receptors and with weak affinity to delta and kappa receptors, with Ki values of 2.1, 57.6 and 42.7 microM, respectively. The pA2 value for naloxone obtained with tramadol in the mouse tail-flick test was 7.76 and was not statistically different from that obtained with morphine (7.94). In CXBK mice, tramadol, like morphine, was devoid of antinociceptive activity after intracerebroventricular administration, suggesting that the opioid component of tramadol-induced antinociception is mediated by the mu-opioid receptor. In contrast to the mouse tail-flick test and unlike morphine or codeine, tramadol-induced antinociception in the mouse abdominal constriction, mouse hot-plate (48 degrees or 55 degrees C) or rat hot-plate tests was only partially antagonized by naloxone, implicating a nonopioid component. Further examination of the neurochemical profile of tramadol revealed that, unlike morphine, it also inhibited the uptake of norepinephrine (Ki = 0.79 microM) and serotonin (0.99 microM). The possibility that this additional activity contributes to the antinociceptive activity of tramadol was supported by the finding that systemically administered yohimbine or ritanserin blocked the antinociception produced by intrathecal administration of tramadol, but not morphine, in the rat tail-flick test. These results suggest that tramadol-induced antinociception is mediated by opioid (mu) and nonopioid (inhibition of monoamine uptake) mechanisms. This hypothesis is consistent with the clinical experience of a wide separation between analgesia and typical opioid side effects.
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              Tramadol: a new centrally acting analgesic.

              The pharmacology, pharmacokinetics, efficacy, adverse effects, and dosage and administration of tramadol are reviewed. 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.
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                Author and article information

                Journal
                Anesth Pain Med
                Anesth Pain Med
                10.5812/aapm
                Kowsar
                Anesthesiology and Pain Medicine
                Kowsar
                2228-7523
                2228-7531
                01 July 2011
                July 2011
                : 1
                : 1
                : 25-29
                Affiliations
                [1 ] Department of Anesthesiology and Pain Medicine, Rasoul-Akram Medical Center, School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran
                [2 ] Department of Anesthesiology, Texas Tech University, Health Science Center, Lubbock, Texas, USA
                Author notes
                [* ] Corresponding author at: Saeid Reza Entezary, Department of Anesthesiology and pain Medicine, Rasoul-Akram Medical Center, School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran. Tel: +98-9121329031, Fax: +98-2166509059. E-mail: sr.entezary@ 123456yahoo.com
                Article
                10.5812/kowsar.22287523.1271
                4335753
                25729652
                e42266ae-5235-437a-823d-f1d93da4b30b
                Copyright © 2011, ISRAPM, Published by Kowsar M.P.Co All rights reserved.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 05 May 2011
                : 12 May 2011
                : 16 May 2011
                Categories
                Research Article

                tramadol,lidocaine,epidural anesthesia,cesarean section
                tramadol, lidocaine, epidural anesthesia, cesarean section

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