Tramadol drug is used for pain relief
Tramadol (generic for Ultram) is a prescription medication used for the management of moderate to moderately severe pain. Tramadol® has been prescribed to more than 55 million patients worldwide; Ultram® has been prescribed to more than 21 million patients in the U.S.

Preemptive ketamine during general anesthesia for postoperative analgesia in patients undergoing laparoscopic cholecystectomy.

[Article in English, Italian]

Launo C, Bassi C, Spagnolo L, Badano S, Ricci C, Lizzi A, Molinino M.

Section of Anesthesia and Intensive Care, Department of Surgery, Anesthesia and Transplants (DISCAT), School of Anesthesia and Intensive Care, University of Genoa, Genoa, Italy.

AIM: Preemptive analgesia is currently in use in the management of postoperative pain and no more under search. The administration of ketamine as intraoperative analgesic agent is well-known since a long time; the analgesic properties of this drug are related to its actions as a non-competitive N-methyl-D-aspartate receptors antagonist; these receptors present an excitatory function on pain transmission and this binding seems to prevent or reverse the central sensitisation of every kind of pain, including postoperative pain. In literature, the use of this anesthetic for the preemptive analgesia in the management of postoperative pain is controversial; for this reason the aim of our study was the clinical evaluation of preemptive perioperative analgesia with low-doses ketamine. METHODS: This trial involved 40 patients undergoing laparoscopic cholecystectomy, with the same surgical operator; postoperative analgesia was performed with the intraoperative administration of ketamine (0.7 mg/kg) or tramadol (15 mg/kg). A randomized, double-blind study was performed; after an inhalatory/analgesic general anesthesia (sevofluorane + remifentanyl) the postoperative-pain control was clinically evaluated through algometric measurements (Visual Analog Scale, Verbal Rating Scale, Pain Intensity Difference); supplemental doses of tramadol were administered if required, also to quantify the adequacy of analgesia, and adverse effects were evaluated. RESULTS: The results show that preemptive intraoperative analgesia with ketamine produces a good analgesia at the awakening, despite low duration (approximately 1 hour), and upgrades the analgesic effect of tramadol in the postoperative period. Among the adverse effects, some (for example nausea) were related to the administration of both analgesics and to the kind of surgery, others (hallucinosis, nystagmus, photophobia, psychomotor excitation, psychotic symptoms) were due to ketamine, and others (respiratory depression and hypotension) could be related to tramadol. Although the adverse effects due to ketamine are more numerous than those related to tramadol, the second could potentially be more dangerous. CONCLUSION: Our study suggests that preemptive low-doses ketamine is able to produce an adequate postoperative analgesia and increases the analgesic effect of tramadol; furthermore, ketamine adverse effects could be reduced by intraoperative administration of benzodiazepines and/or antiemetic drugs, or by the association of ketamine and a peripheral analgesic (ketorolac).
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15516884&query_hl=2

Clinical pharmacology of tramadol.

Grond S, Sablotzki A.

Department of Anesthesia, Martin-Luther-University, Halle-Wittenberg, Germany. Stefan.grond@medizin.uni-halle.de

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.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15509185&query_hl=2

The postoperative analgesic effect of tramadol when used as subcutaneous local anesthetic.

Altunkaya H, Ozer Y, Kargi E, Ozkocak I, Hosnuter M, Demirel CB, Babuccu O.

Department of Anesthesiology, Zonguldak Karaelmas University, School of Medicine, Ev-Ko Konutlari F-66 No: 8, 67600 Kozlu/Zonguldak, Turkey. haltunkaya@hotmail.com

Recently, it has been shown that tramadol was an effective local anesthetic in minor surgery. In this study, its efficacy for relieving postoperative pain was evaluated. Forty patients undergoing minor surgery (lipoma excision and scar revision) under local anesthesia were included. The patients were randomly allocated into two groups: In group T (n = 20), 2 mg/kg tramadol, and in group L (n = 20), 1 mg/kg lidocaine were given subcutaneously. In both groups, the injection volume was 5 mL containing 1/200,000 adrenalin. The degree of the erythema, burning sensation, and pain at the injection site were recorded. Incision response, which is a degree of the pain sensation during incision, was recorded and graded with the visual analog scale (VAS) 0-10. After incision, VAS values were recorded at 15-min intervals. When the VAS score of the pain during surgery exceeded 4, an additional 0.5 mg/kg of the study drug was injected and this dosage was added to the total amount. Patients were discharged on the same day. Subjects with VAS > or =4 were advised to take paracetamol as needed. No side effects were recorded in either group except for 1 patient complaining of nausea in group T at the 30th min of operation. After 24 h, patients were called and the time of first analgesic use and total analgesic dose taken during the postoperative period were recorded. During the 24 postoperative hours, 18 of 20 (90%) subjects did not need any type of analgesia in group T, whereas this number was 10 (50%) in group L (P < 0.05). The time span before taking first analgesic medication was longer (4.9 +/- 0.3 h) in group T than that of group L (4.4 +/- 0.7 h) (P < 0.05). We propose that tramadol can be used as an alternative drug to lidocaine for minor surgeries because of its ability to decrease the demand for postoperative analgesia.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15502049&query_hl=2

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