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      Comparison of tramadol/acetaminophen fixed-dose combination, tramadol, and acetaminophen in patients undergoing ambulatory arthroscopic meniscectomy

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          Abstract

          Objectives

          Preemptive analgesia is a technique in which analgesics are administered before a surgery to provide better postoperative pain relief with fewer side effects. In this study, we aimed to compare the preemptive efficacy of tramadol/acetaminophen fixed-dose combination, tramadol, and acetaminophen in patients undergoing ambulatory arthroscopic partial meniscectomy.

          Methods

          We evaluated the patient records of 75 patients who underwent ambulatory arthroscopic partial meniscectomy. We divided the patients into three groups consisting of 20 patients each to equalize the groups. Group A comprised patients who were administered 37.5 mg tramadol/325 mg acetaminophen fixed-dose combination, Group B comprised patients who were administered 50 mg tramadol, and Group C comprised patients who were administered 500 mg acetaminophen. Premedication was not used in any group.

          Results

          There were no significant differences between the groups in terms of age, sex, BMI, and duration of surgery and anesthesia. All patients in Group B and Group C and 17 patients in Group A required rescue analgesics in the first 6 h. Visual analog scale (VAS) was 4.75 ± 3.05 in Group B at time 0 and was 6.10 ± 1.86 in Group C in the first hour and was higher than the other groups with a statistically significance (p = 0.030 and 0.020, respectively). VAS at 24 h postoperatively was ≤3 (1.60 ± 1.63, 1.55 ± 1.84 and 1.70 ± 0.65 respectively in each group), and none of the patients in any group required rescue analgesics. No major side effects, except for slight nausea in one patient requiring no medication, were noted in any group.

          Conclusion

          The fixed-dose combination of tramadol/acetaminophen or tramadol alone is better than acetaminophen alone as a preemptive analgesic in patients undergoing ambulatory arthroscopic meniscectomy.

          Level of evidence

          Level III, therapeutic study.

          Related collections

          Most cited references25

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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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            Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man.

            For more than three decades, acetaminophen (INN, paracetamol) has been claimed to be devoid of significant inhibition of peripheral prostanoids. Meanwhile, attempts to explain its action by inhibition of a central cyclooxygenase (COX)-3 have been rejected. The fact that acetaminophen acts functionally as a selective COX-2 inhibitor led us to investigate the hypothesis of whether it works via preferential COX-2 blockade. Ex vivo COX inhibition and pharmacokinetics of acetaminophen were assessed in 5 volunteers receiving single 1000 mg doses orally. Coagulation-induced thromboxane B(2) and lipopolysaccharide-induced prostaglandin E(2) were measured ex vivo and in vitro in human whole blood as indices of COX-1 and COX-2 activity. In vitro, acetaminophen elicited a 4.4-fold selectivity toward COX-2 inhibition (IC(50)=113.7 micromol/L for COX-1; IC(50)=25.8 micromol/L for COX-2). Following oral administration of the drug, maximal ex vivo inhibitions were 56% (COX-1) and 83% (COX-2). Acetaminophen plasma concentrations remained above the in vitro IC(50) for COX-2 for at least 5 h postadministration. Ex vivo IC(50) values (COX-1: 105.2 micromol/L; COX-2: 26.3 micromol/L) of acetaminophen compared favorably with its in vitro IC(50) values. In contrast to previous concepts, acetaminophen inhibited COX-2 by more than 80%, i.e., to a degree comparable to nonsteroidal antiinflammatory drugs (NSAIDs) and selective COX-2 inhibitors. However, a >95% COX-1 blockade relevant for suppression of platelet function was not achieved. Our data may explain acetaminophen's analgesic and antiinflammatory action as well as its superior overall gastrointestinal safety profile compared with NSAIDs. In view of its substantial COX-2 inhibition, recently defined cardiovascular warnings for use of COX-2 inhibitors should also be considered for acetaminophen.
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              Multimodal analgesia for controlling acute postoperative pain.

              Multimodal analgesia is needed for acute postoperative pain management due to adverse effects of opioid analgesics, which can impede recovery; a problem that is of increasing concern with the rapid increase in the number of ambulatory surgeries. Yet, the literature on multimodal analgesia often shows variable degrees of success, even with studies utilizing the same adjuvant medication. Nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors consistently reduce postoperative opioid consumption. The N-methyl-D-aspartate antagonists have produced variable results in studies, which may be due to the dose and timing of drug administration. Alpha-2 adrenergic agonists have been useful as adjuvant for regional analgesia but not when administered orally. The alpha-2-delta receptor modulators such as gabapentin have shown early promising results in multimodal analgesia. Local anesthetic injection at the surgical site, though not as a preemptive analgesic, has recently been demonstrated to be beneficial in multimodal analgesia. No new adjuvants have appeared in the last year, which robustly reduce opioid consumption and opioid-related adverse effects. There is a continuing need to explore new drug combinations to achieve all of the purported goals of multimodal anesthesia.
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                Author and article information

                Contributors
                Journal
                Acta Orthop Traumatol Turc
                Acta Orthop Traumatol Turc
                Acta Orthopaedica et Traumatologica Turcica
                Turkish Association of Orthopaedics and Traumatology
                1017-995X
                2589-1294
                26 March 2018
                May 2018
                26 March 2018
                : 52
                : 3
                : 222-225
                Affiliations
                [a ]Süleyman Demirel University School of Medicine Anaesthesiology and Reanimation Department, Turkey
                [b ]Süleyman Demirel University School of Medicine Orthopaedics and Traumatology Department, Turkey
                Author notes
                []Corresponding author. Süleyman Demirel Üniversitesi Tıp Fakültesi Ortopedi ve Travmatoloji Anabilim Dalı, Çünür, Isparta, Turkey. Tel.: +90 533 234 6280. emrahkovalak@ 123456yahoo.com
                Article
                S1017-995X(17)30348-6
                10.1016/j.aott.2018.02.011
                6136315
                29598842
                142be9ac-d332-48c1-a0f2-44c25f38d30d
                © 2018 Turkish Association of Orthopaedics and Traumatology. Publishing services by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 8 June 2017
                : 5 February 2018
                : 26 February 2018
                Categories
                Research Paper

                preemptive analgesia,arthroscopic meniscectomy,tramadol,acetaminophen,pacu, post-anesthesia care unit,nnt, number needed to treat,bmi, body mass index

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