Minerva Anestesiol. 2004 Sep;70(9):661-9.

Immediate postoperative pain management in patients undergoing major abdominal surgery after remifentanil-based anesthesia: sufentanil vs tramadol.

Cafiero T, Di Minno RM, Sivolella G, Di Iorio C.

Department of Anesthesia, Postoperative Intensive Care, Burn Center and Hyperbaric Center A. Cardarelli Hospital, Naples, Italy.

AIM: The transition from intraoperative analgesia to postoperative analgesia must be planned carefully after remifentanil-based anesthesia, due to the short duration of action of remifentanil. The aim of this study is to compare the efficacy and safety of 2 transition strategies using sufentanil or tramadol for early postoperative pain relief in patients who had major abdominal surgery under general anesthesia with remifentanil/sevoflurane. METHODS: Sixty patients participated in this double-blind, prospective study and were randomly assigned to either sufentanil (S) group or tramadol (T) group. Twenty minutes before the end of surgery the patients received either a bolus of 0.15 microg kg(-1) sufentanil (group S) or tramadol 100 mg (group T). Mean arterial pressure (MAP), heart rate (HR) and rate pressure product (RPP=systolic arterial pressure (SAP)xHR), analgesia by a verbal rating score (VRS) and sedation by a sedation score (SS) were evaluated at emergence from anesthesia. RESULTS: A statistically significant difference in HR between the 2 groups was recorded at extubation (78+/-13 in group S vs 86+/-24 in group T). A significant decrease of RPP values at extubation and 5 minutes later were found in group S in comparison with group T. VRS values were significantly lower in sufentanil group at 5 and 10 minutes after awakening. CONCLUSIONS: Sufentanil provided more effective transition analgesia in comparison with tramadol. The effects of remifentanil dissipated rapidly and analgesia with major opioids was required. A bolus dose of sufentanil 0.15 microg kg(-1) was efficacious in controlling the hemodynamic parameters at awakening from anesthesia. The lower HR values and, consequently the lower RPP values are of utmost importance especially in the aged cardiovascular risk patient.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15467498




Pharmacoepidemiol Drug Saf. 2004 Apr 23

Impact of mailed warning to prescribers on the co-prescription of tramadol and antidepressants.

Shatin D, Gardner JS, Stergachis A, Blough D, Graham D.

Center for Health Care Policy and Evaluation, UnitedHealth Group, Minneapolis, MN, USA.

PURPOSE: An evaluation was made of the effectiveness in changing prescribing behavior of 'Dear Health Professional (DHP)' letters mailed by the manufacturer to physicians and other health professionals advising them of safety information on co-prescribing of tramadol and antidepressants. METHODS: A retrospective cohort analysis of prescription claims of all plan members from 12 UnitedHealth Group-affiliated health plans who received a first prescription for tramadol between 1 April 1995 and 31 December 1996. The prevalence of co-prescribing of antidepressants and tramadol relative to the date of the 'DHP' communication was determined. RESULTS: 9218 plan members received an initial prescription for tramadol within the observation period. Prior to the date of the 'DHP' communication 1061/4774 (22.2%) members received a prescription for an antidepressant within 30 days of their first prescription for tramadol. Following the date of the communication 844/4444 (19.0%) of members received an antidepressant within 30 days of their first prescription for tramadol. An overall decreasing linear trend in antidepressant co-prescribing was evident over the observation period, but there was no statistically significant acceleration in the decrease following this communication. CONCLUSIONS: The mailed 'DHP' advisory letter did not affect the rate of co-prescribing of tramadol with antidepressants.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15386714




Biomed Chromatogr. 2004 Oct;18(8):589-99.

Quality assessment for tramadol in pharmaceutical preparations with thin layer chromatography and densitometry.

Krzek J, Starek M.

Jagiellonian University, Collegium Medicum, Department of Inorganic and Analytical Chemistry, 9 Medyczna Str., 30-688 Krakow, Poland.

Research studies have been carried out to develop a chromatographic and densitometric method suitable for identification and determination of tramadol and impurities. In addition, the stability of tramadol in solutions was investigated, including an effect of solution pH, temperature and incubation time. In the first instance the conditions for identification and quantitative determination of tramadol and impurities in pharmaceutical preparations were established. The separation was performed on silica gel-coated chromatographic plates (HPTLC) using two mobile phases: (I) chloroform-methanol-glacial acetic acid (9:2:0.1, v/v/v); (II) chloroform-toluene-ethanol (9:8:1, v/v/v). The UV densitometry was carried out at lambda = 270 nm. The developed method is of high sensitivity and low detection and determination limits ranging from 0.044 to 0.35 microg. For individual constituents the recovery ranges from 93.23 to 99.66%. The next step was to evaluate the stability of tramadol and determine a method of decomposition under various experimental conditions. It was found that tramadol decomposes in various ways in acidic and basic environments producing (1RS)-[2-(3-methoxyphenyl)cyclohex-2-enyl]-N,N-dimethylmethanamine (imp. B) and (1RS, 2RS)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol (imp. cis-T) or imp. cis-T, respectively.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15386511




J Rheumatol. 2004 Dec;31(12):2454-63.

Analgesic efficacy and safety of tramadol/ acetaminophen combination tablets (Ultracet) in treatment of chronic low back pain: a multicenter, outpatient, randomized, double blind, placebo controlled trial.

Peloso PM, Fortin L, Beaulieu A, Kamin M, Rosenthal N; Protocol TRP-CAN-1 Study Group.

Division of Rheumatology, Roy and Lucille Carver College of Medicine, University of Iowa Health Care E330 GH, 200 Hawkins Drive, Iowa City, IA 52242, USA.

OBJECTIVE: To evaluate the analgesic efficacy and safety of tramadol 37.5 mg/acetaminophen 325 mg (tramadol/APAP) combination tablets for treatment of chronic low back pain (LBP). METHODS: This 91 day, multicenter, outpatient, randomized, double blind, placebo controlled study enrolled 338 patients with chronic LBP requiring daily medication for > or = 3 months. Patients with at least moderate pain [pain visual analog scale (VAS) with scores > or = 40/100 mm] after washout were randomized to tramadol/APAP or placebo. After a 10 day titration, patients received 1 or 2 tablets QID. Primary outcome measure was final pain VAS score. Secondary measures included pain relief, quality of life and physical functioning, efficacy failure, and overall medication assessments. RESULTS: In total, 336 intent-to-treat patients received tramadol/APAP (n = 167) or placebo (n = 169). Mean baseline pain VAS score was 67.8. Intent-to-treat analysis showed significantly better mean final pain VAS scores (47.4 vs 62.9; p < 0.001) and mean final pain relief scores (1.8 vs 0.7; p < 0.001) for tramadol/APAP than for placebo. Roland Disability Questionnaire scores and physical-related subcategories of the McGill Pain Questionnaire and the Medical Outcome Study Short Form-36 Health Survey were significantly better for tramadol/APAP patients. More patients rated tramadol/APAP as "very good" or "good" than placebo (63.6 vs 25.2%; p < 0.001). Kaplan-Meier estimates of cumulative discontinuation rates due to efficacy failures were 22.9% (tramadol/APAP) vs 54.7% (placebo; p < 0.001). The most common treatment related adverse events with tramadol/APAP were nausea (12.0%), dizziness (10.8%), and constipation (10.2%). Average daily dose of tramadol/APAP was 4.2 tablets (tramadol 158 mg/APAP 1369 mg). CONCLUSION: Tramadol 37.5 mg/APAP 325 mg combination tablets show efficacy in pain reduction, in measures of physical functioning and quality of life, and in overall medication assessments, with a tolerability profile comparable with other opioids used for the treatment of chronic LBP.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15570651




Yao Xue Xue Bao. 2004 Jun;39(6):458-62.

Determination of tramadol and its active metabolite O-desmethyltramadol in plasma and amniotic fluid using LC/MS/MS

Zhao LM, Chen XY, Cui JJ, Sunita M, Zhong DF.

Laboratory of Clinical Pharmacology, China Medical University No. 2 Hospital, Shenyang 110004, China.

AIM: To determinate tramadol and O-desmethyltramadol in human plasma and amniotic fluid by LC/MS/MS, and distribution of tramadol and O-desmethyltramadol in maternity and fetus were studied. METHODS: Samples containing tramadol, O-desmethyltramadol and diphenhydramine (internal standard, IS ) were extracted using liquid-liquid extraction, followed by liquid chromatographic separation and on-line MS/MS using atmospheric pressure chemical ionization as an interface detection. The analytes were detected in the selected reaction monitoring mode. RESULTS: The calibration curves for tramadol and O-desmethytramadol in plasma and amniotic fluid were linear in the range from 8.0 to 800.0 microg x L(-1) (plasma) and 1.0 to 400.0 microg x L(-1) (amniotic fluid). The method was applied to the measurement of tramadol and O-desmethytramadol concentrations in maternal vein, umbilical vein, umbilical artery and amniotic fluid. Following intramuscular pre-operative administration 1.5 mg x kg(-1) doses of tramadol to parturients, plasma concentrations of tramadol were significantly higher than those in amniotic fluid. The concentrations of O-desmethyltramadol in plasma were lower, and were not detected in amniotic fluid. CONCLUSION: The method is shown to be accurate, robust and convenient, and suitable for clinical pharmacokinetics studies of tramadol and O-desmethyltramadol.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15491106