BACKGROUND: Spontaneous adverse drug reaction (ADR) reporting data has been used for safety of post-market drug surveillance. A system has been required that is able to detect signals associated with drugs by analyzing the collected ADR data. METHODS: We developed the web-based automated analysis system (ADR-detector). We used the data which reported ADR spontaneously between March 2009 and December 2010 to Korean Food and Drug Administration. We used 3 statistical indicators for evaluating ADR signals: proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). The ADR reports which were detected as significant signals based on the indicators have been reviewed. RESULTS: Among 153,774 reports, 9,955 cases were related to 4 analgesics which were most frequently reported analgesic drugs during the study period. The numbers of ADR reports associated with each drug are as follow: 5,623 reports in tramadol (56.5 %), 1,720 reports in fentanyl (17.3 %), 1,463 reports in tramadol-combination (14.7 %), and 1,149 reports in ketorolac (11.5 %). Top 5 ADR were nausea (3,351 reports - 33.7 %), vomiting (1,755 reports - 17.6 %), dizziness (1,130 - 11.4 %), rash (412 reports - 4.1 %), and pruritus (354 reports - 3.6 %). 6,674 ADR reports were significant based on PRR and ROR, and 336 reports were significant based on IC. CONCLUSION: By using the automated analysis system, not only statisticians but also general researchers are able to analyze ADR signals in real-time. Also ADR-detector would provide rapid review and cross-check of ADR.
Analgesics ; Data Mining ; Dizziness ; Drug Toxicity ; Exanthema ; Fentanyl ; Ketorolac ; Nausea ; Odds Ratio ; Pruritus ; Tramadol ; United States Food and Drug Administration ; Vomiting

OBJECTIVETo evaluate the safety and analgesic efficacy of patient controlled intravenous analgesia (PCIA) with tramadol, and to compare its benefits and risks with combined spinal-epidural analgesia (CSEA)+ patient controlled epidural analgesia (PCEA).

METHODSEighty 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).

RESULTSBoth 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.

CONCLUSIONSPCIA 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.

Adult ; Analgesia, Obstetrical ; methods ; Analgesia, Patient-Controlled ; Analgesics, Opioid ; administration & dosage ; Female ; Humans ; Pain ; prevention & control ; Pain Measurement ; Pregnancy ; Safety ; Tramadol ; administration & dosage

PURPOSE: Optimal analgesia in ambulatory urology patients still remains a challenge. The aim of this study was to examine if the pre-emptive use of intravenous tramadol can reduce pain after ureteroscopic lithotripsy in patients diagnosed with unilateral ureteral stones. MATERIALS AND METHODS: This prospective pilot cohort study included 74 patients diagnosed with unilateral ureteral stones who underwent ureteroscopic lithotripsy under general anesthesia in the Urology Clinic at the Clinical Center of Serbia from March to June 2012. All patients were randomly allocated to two groups: one group (38 patients) received intravenous infusion of tramadol 100 mg in 500 mL 0.9%NaCl one hour before the procedure, while the other group (36 patients) received 500 mL 0.9%NaCl at the same time. Visual analogue scale (VAS) scores were recorded once prior to surgery and two times after the surgery (1 h and 6 h, respectively). The patients were prescribed additional postoperative analgesia (diclofenac 75 mg i.m.) when required. Pre-emptive effects of tramadol were assessed measuring pain scores, VAS1 and VAS2, intraoperative fentanyl consumption, and postoperative analgesic requirement. RESULTS: The average VAS1 score in the tramadol group was significantly lower than that in the non-tramadol group. The difference in average VAS2 score values between the two groups was not statistically significant; however, there were more patients who experienced severe pain in the non-tramadol group (p<0.01). The number of patients that required postoperative analgesia was not statistically different between the groups. CONCLUSION: Pre-emptive tramadol did reduce early postoperative pain. The patients who received pre-emptive tramadol were less likely to experience severe post-operative pain.
Adult ; Analgesics, Opioid/*administration & dosage/therapeutic use ; Female ; Humans ; *Lithotripsy ; Male ; Middle Aged ; Pain/*prevention & control ; Pain Measurement ; Tramadol/*administration & dosage/therapeutic use ; *Ureteroscopy

This study was performed to evaluate the sedative and analgesic effects of xylazine (X) and tramadol (T) intravenously (IV) administered to horses. Six thoroughbred saddle horses each received X (1.0 mg/kg), T (2.0 mg/kg), and a combination of XT (1.0 and 2.0 mg/kg, respectively) IV. Heart rate (HR), respiratory rate (RR), rectal temperature (RT), indirect arterial pressure (IAP), capillary refill time (CRT), sedation, and analgesia (using electrical stimulation and pinprick) were measured before and after drug administration. HR and RR significantly decreased from basal values with X and XT treatments, and significantly increased with T treatment (p < 0.05). RT and IAP also significantly increased with T treatment (p < 0.05). CRT did not change significantly with any treatments. The onset of sedation and analgesia were approximately 5 min after both X and XT treatments; however, the XT combination produced a longer duration of sedation and analgesia than X alone. Two horses in the XT treatment group displayed excited transient behavior within 5 min of drug administration. The results suggest that the XT combination is useful for sedation and analgesia in horses. However, careful monitoring for excited behavior shortly after administration is recommended.
Analgesics, Opioid/administration & dosage/*pharmacology ; Animals ; Blood Pressure ; Drug Therapy, Combination ; Female ; Heart Rate ; Horses/*physiology ; Hypnotics and Sedatives/administration & dosage/*pharmacology ; Male ; Respiratory Rate ; Tramadol/administration & dosage/*pharmacology ; Xylazine/administration & dosage/*pharmacology

PURPOSE: Transrectal ultrasound-guided prostate biopsy is the procedure of choice for diagnosing prostate cancer. We compared with pain-relieving effect of acetaminophen, a known drug for enhancing the pain-relieving effect of tramadol, and eutectic mixture of local anesthetics (EMLA), a local anesthetic agent, with that of the conventional periprostatic nerve block method. MATERIALS AND METHODS: This was a prospective, randomized, single-blinded study. A total of 430 patients were randomly assigned to three groups. Group 1 received a periprostatic nerve block with 1% lidocaine, group 2 received acetaminophen 650 mg, and group 3 received EMLA cream for pain control. All patients were given 50 mg of tramadol intravenously 30 minutes before the procedure. At 3 hours after completion of the procedure, the patients were asked to grade their pain on a horizontal visual analogue scale (VAS). The patients were also asked whether they were willing to undergo future biopsy if required. RESULTS: There were no significant differences between the three groups in terms of age, prostate-specific antigen, prostate size, or numbers of biopsy cores. The pain scores for groups 2 and group 3, which were 3.47+/-1.92 and 3.50+/-1.36, respectively, were similar and were significantly lower than that of group 1, which was 5.24+/-2.07. CONCLUSIONS: Acetaminophen and EMLA cream with intravenous injection of tramadol are safe, easy, and effective methods of controlling pain during the procedure. These methods were more effective for pain relief than was the conventional periprostatic nerve block method.
Acetaminophen ; Administration, Oral ; Anesthetics, Local ; Biopsy ; Biopsy, Needle ; Humans ; Injections, Intravenous ; Lidocaine ; Nerve Block ; Prilocaine ; Prospective Studies ; Prostate ; Prostate-Specific Antigen ; Prostatic Neoplasms ; Tramadol

The present study investigated whether a co-application of tramadol (TRA) and dihydroetorphine (DHE) would exert a synergy in analgesic effect and delay acute tolerance development. Intraperitoneal injection of TRA (in mg) and subcutaneous injection of DHE (in ng) were delivered in fixed proportions (1:6.25, 1:12.5, 1:25, 1:50, 1:100, and 1:200). The effect of analgesia was accessed by tail-flick test and analyzed with isobolographic analysis. For test of acute tolerance, six successive injections of either TRA (20 mg/kg) alone, DHE (1 000 ng/kg) alone, or a combination of TRA (20 mg/kg) and DHE (250 ng/kg) were administered. We found that (1) except for 1 mg : 6.25 ng and 1 mg : 50 ng, combinations, all the other ratios produced a significant synergy in their analgesic effect; (2) the effect of analgesia induced by repeated TRA plus DHE injections lasted significantly longer, indicating a slower onset of acute tolerance. These results indicate that TRA and DHE injections in certain dose ratios can induce synergistic analgesia, which is resistant against the development of acute tolerance.
Analgesics, Opioid ; administration & dosage ; pharmacology ; Animals ; Drug Synergism ; Drug Tolerance ; physiology ; Etorphine ; administration & dosage ; analogs & derivatives ; pharmacology ; Female ; Male ; Pain ; drug therapy ; physiopathology ; Rats ; Rats, Wistar ; Tramadol ; administration & dosage ; pharmacology

Adult ; Analgesics, Opioid ; administration & dosage ; pharmacology ; Anesthesia, General ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Neurosurgical Procedures ; Postoperative Complications ; drug therapy ; prevention & control ; Shivering ; drug effects ; Tramadol ; administration & dosage ; therapeutic use

Tramadol and its metabolites in rat urine were identified by LC-MS(n). Rat urine samples of 0-36 h were collected after ip 9.0 mg x kg(-1) tramadol, then the samples were enriched and purified through solid-phase extraction cartridge. Purified samples were analyzed by LC-MS(n). Possible metabolites were discovered by comparing the full scan and SIM chromatograms of the test samples with the corresponding blanks and analyzing the retention time, quasi-molecular ion and fragment ion of all chromatograms. Nine phase I metabolites and four phase II metabolites were identified in rat urine. One of the metabolites was found first time in living body. The metabolites were formed via the following metabolic pathways: O-demethylation, N-demethylation, hydroxylation, N-oxidation and conjugation. The method can be used to identify tramadol and its metabolites in other animals and human.
Analgesics, Opioid ; administration & dosage ; metabolism ; urine ; Animals ; Chromatography, High Pressure Liquid ; Injections, Intraperitoneal ; Male ; Rats ; Rats, Wistar ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry ; Tramadol ; administration & dosage ; metabolism ; urine

OBJECTIVE: To observe postoperative analgesia and preemptive analgesia of Tramadol hydrochloride sustained release tablets for nasal endoscopic operation. METHOD: A total of 188 patients undergoing nasal endoscopic operation were randomized into the experimental group and control group, with 94 patients in each group. Each patient in experimental group was gaved on Tramadol hydrochloride sustained release tablets at 12h, 24h, 48h, postoperation and before the cleaning up procession respectively, the control group was not administered. VAS scores were observed at 12, 24, and 48 hours after operation. The discomfort reaction during postoperation and cleaning up procession such as insomnia, impatien, nervous, frightening, syncope and shock were also observed and recorded. RESULT: Visuala analogue scale scores of the experimental groups after 12, 24 hours and 48h were significantly lower than the control group. The discomfort reaction appear more frequently in control group. CONCLUSION Tramadol hydrochloride sustained release tablets effectively relieves postoperative pain of nasal endoscopic operation. It can also decrease the discomfort reaction during postoperation and cleaning up procession and facilitate recovering of patients.
Adolescent ; Adult ; Analgesics, Opioid ; administration & dosage ; therapeutic use ; Delayed-Action Preparations ; Endoscopy ; methods ; Female ; Humans ; Male ; Middle Aged ; Nasal Surgical Procedures ; methods ; Pain Measurement ; Pain, Postoperative ; drug therapy ; Postoperative Period ; Tramadol ; administration & dosage ; therapeutic use ; Young Adult

OBJECTIVE: To evaluate the effect of intrathecal pumping tramadol on cell-mediated immunity in rats with formalin inflammatory pain. METHODS: Thirty-two Sprague-Dawley adult male rats weighting 250 approximately 300 g were randomly divided into 4 groups (n=8 in each group):Saline group (NS) and 3 tramadol groups (T1,T2,and T3). The rats were anesthetized with intraperitoneal chloral hydrate (300 approximately 350)mg/kg. Microspinal catheter was inserted into the subarachnoid space at the lumber region according to modified Yaksh techniques. In the tramadol groups,after 5 days tramadol was continuously infused through the spinal catheter at 50 (T1),25 (T2), and 12.5 microg/h (T3) for 7 days. In the NS group normal saline was continuously infused instead of tramadol. On Day 7 formalin (5%, 50 microL) was injected into the plantar surface of the left hindpaw. The number of flinches, lickings and total time of licking was recorded for 60 min.Pain intensity scoring(PIS)(0 approximately 3;0= no pain, 3=severe pain) was used to assess the antinociceptive effect of intrathecal tramadol. The rats were killed after the evaluation of pain intensity. Body weight and spleen weight were measured and spleen index (spleen weight/body weight) was calculated. T-lymphocyte function was evaluated based on Concanavalin-A(ConA) induced splenocyte proliferation. A modified lactic acid dehydrogenase(LDH) release assay was done to assess the NK cell activity. Phenotypic expressions of cell surface markers of T lymphocyte subsets (CD3+, CD3+ CD4+, CD3+ CD8+, and CD4+/ CD8+) and NK cell(CD161+) in the spleen were analyzed by flow cytometry. RESULTS: The PIS scores were significantly lower in the T1,T2,and T3 groups than those in the NS group. The spleen index and splenocyte proliferation induced by ConA were significantly suppressed in the T1 group,and the phenotypes of T lymphocyte subsets were significantly changed,but no significant difference was found in the T2 and T3 groups compared with the NS group. There were no differences in NK cell activity in the 3 tramadol groups from the control group. CONCLUSION Intrathecal pumping tramadol has significantly antinociceptive effect. Intrathecal pumping higher dosage tramadol (50microg/h) suppresses T lymphocyte proliferation and alteres T lymphocyte subset phenotype but does not affect NK cell activity. General analgesic dosage tramadol (25 and 12.5 microg/h) has no effect on the immune function.
Analgesics, Opioid ; pharmacology ; Animals ; Dose-Response Relationship, Drug ; Formaldehyde ; Injections, Spinal ; Killer Cells, Natural ; immunology ; Male ; Pain ; chemically induced ; immunology ; Pain Measurement ; drug effects ; Rats ; Rats, Sprague-Dawley ; T-Lymphocyte Subsets ; immunology ; Tramadol ; administration & dosage ; pharmacology