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

PURPOSE: Postoperative ileus (POI) is common following bowel resection for radical cystectomy with ileal conduit (RCIC). We investigated perioperative factors associated with prolonged POI following RCIC, with specific focus on opioid-based analgesic dosage. MATERIALS AND METHODS: From March 2007 to January 2013, 78 open RCICs and 26 robot-assisted RCICs performed for bladder carcinoma were identified with adjustment for age, gender, American Society of Anesthesiologists grade, and body mass index (BMI). Perioperative records including operative time, intraoperative fluid excess, estimated blood loss, lymph node yield, and opioid analgesic dose were obtained to assess their associations with time to passage of flatus, tolerable oral diet, and length of hospital stay (LOS). Prior to general anaesthesia, patients received epidural patient-controlled analgesia (PCA) consisted of fentanyl with its dose adjusted for BMI. Postoperatively, single intravenous injections of tramadol were applied according to patient desire. RESULTS: Multivariate analyses revealed cumulative dosages of both PCA fentanyl and tramadol injections as independent predictors of POI. According to surgical modality, linear regression analyses revealed cumulative dosages of PCA fentanyl and tramadol injections to be positively associated with time to first passage of flatus, tolerable diet, and LOS in the open RCIC group. In the robot-assisted RCIC group, only tramadol dose was associated with time to flatus and tolerable diet. Compared to open RCIC, robot-assisted RCIC yielded shorter days to diet and LOS; however, it failed to shorten days to first flatus. CONCLUSION: Reducing opioid-based analgesics shortens the duration of POI. The utilization of the robotic system may confer additional benefit.
Aged ; Analgesics, Opioid/*administration & dosage/therapeutic use ; Carcinoma/*surgery ; Cystectomy/*adverse effects ; Dose-Response Relationship, Drug ; Female ; Humans ; Ileus/*epidemiology ; Length of Stay ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Robotic Surgical Procedures/adverse effects ; Time Factors ; Tramadol/*administration & dosage/therapeutic use ; Treatment Outcome ; Urinary Bladder Neoplasms/*surgery ; Urinary Diversion/*adverse effects

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

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

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

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

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

BACKGROUNDEarly studies showed that naloxone infusion decreases the incidence of morphine-related side effects from intravenous patient-controlled analgesia. This study aimed to determine whether naloxone preserved analgesia while minimizing side effects caused by intravenous tramadol administration.

METHODSEighty patients undergoing general anesthesia for cervical vertebrae surgery were randomly divided into four groups. All patients received 1 mg/kg tramadol 30 minutes before the end of surgery, followed by a continuous infusion with 0.3 mg x kg(-1) x h(-1) tramadol with no naloxone (group I, n = 20), 0.05 microg x kg(-1) x h(-1) naloxone (group II, n = 20), 0.1 microg x kg(-1) x h(-1) naloxone (group III, n = 20) and 0.2 microg x kg(-1) x h(-1) naloxone (group IV, n = 20). Visual analog scales (VAS) for pain during rest and cough, nausea five-point scale (NFPS) for nausea and vomiting, and ramsay sedation score (RSS) for sedation were assessed at 2, 6, 12, 24 and 48 hours postoperatively. Analgesia and side effects were evaluated by blinded observers.

RESULTSSeventy-eight patients were included in this study. The intravenous tramadol administration provided the satisfied analgesia. There was no significant difference in either resting or coughing VAS scores among naloxone groups and control group. Compared with control group, sedation was less in groups II, III, and IV at 6, 12, and 24 hours (P < 0.05); nausea was less in groups II, III and IV than group I at 2, 6, 12, 24 and 48 hours postoperatively (P < 0.05). The incidence of vomiting in the control group was 35% vs. 10% for the highest dose naloxone group (group IV) (P < 0.01).

CONCLUSIONA small-dose naloxone infusion could reduce tramadol induced side effects without reversing its analgesic effects.

Analgesia, Patient-Controlled ; methods ; Analgesics, Opioid ; administration & dosage ; adverse effects ; therapeutic use ; Anesthesia, General ; methods ; Cervical Vertebrae ; surgery ; Female ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Naloxone ; administration & dosage ; adverse effects ; therapeutic use ; Narcotic Antagonists ; administration & dosage ; adverse effects ; therapeutic use ; Nausea ; chemically induced ; Tramadol ; administration & dosage ; adverse effects ; therapeutic use

OBJECTIVE: To develop a rapid and accurate gas chromatography method and investigate the distribution of tramadol in acute poisoned rats for information of samples selection and results evaluation in forensic identification. METHODS: After an oral administration of tramadol at 1140 mg/kg (5 x LD50), concentrations of tramadol in rats' biological fluids and tissues were determined by gas chromatography. RESULTS: The limit of detection of tramadol in blood and urine was 0.1 microg/mL and the limit of detection in liver was 0.1 microg/g. The intra-day precision and inter-day precision were within 3.1% and 5.5% respectively, and the recovery of tramadol in blood was more than 98%. The average levels of tramadol displayed in descending order of heart blood, liver, peripheral blood, urine, vitreous humor, kidney, lung, spleen, heart, brain respectively. CONCLUSION The established method could meet the requirements for toxicological analysis, and the results of the study suggest that blood, urine, liver, lung and kidney are suitable samples for forensic toxicological analysis in tramadol poisoning cases.
Acute Disease ; Administration, Oral ; Analgesics, Opioid/urine* ; Animals ; Body Fluids/chemistry* ; Chromatography, Gas/methods* ; Kidney/metabolism* ; Liver/metabolism* ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Sensitivity and Specificity ; Substance Abuse Detection/methods* ; Tissue Distribution ; Tramadol/urine*

BACKGROUND/AIMS: Acidic saline injections produce mechanical hyperresponsiveness in male Sprague-Dawley rats. We investigated the effect of milnacipran in conjunction with tramadol on the pain threshold in an acidic saline animal model of pain. METHODS: The left gastrocnemius muscle of 20 male rats was injected with 100 microL of saline at pH 4.0 under brief isoflurane anesthesia on days 0 and 5. Rats administered acidic saline injections were separated into four study subgroups. After determining the pre-drug pain threshold, rats were injected intraperitoneally with one of the following regimens; saline, milnacipran alone (60 mg/kg), milnacipran (40 mg/kg) plus tramadol (20 mg/kg), or milnacipran (40 mg/kg) plus tramadol (40 mg/kg). Paw withdrawal in response to pressure was measured at 30 min, 120 min, and 5 days after injection. Nociceptive thresholds, expressed in grams, were measured with a Dynamic Plantar Aesthesiometer (Ugo Basile, Italy) by applying increasing pressure to the right or left hind paw until the rat withdrew the paw. RESULTS: A potent antihyperalgesic effect was observed when tramadol and milnacipran were used in combination (injected paw, p=0.001; contralateral paw, p=0.012). This finding was observed only at 30 min after the combination treatment. CONCLUSIONS: We observed potentiation of the antihyperalgesic effect when milnacipran and tramadol were administered in combination in an animal model of fibromyalgia. Further research is required to determine the efficacy of various combination treatments in fibromyalgia in humans.
Analgesics, Opioid/administration & dosage/*pharmacology ; Animals ; Antidepressive Agents/administration & dosage/*pharmacology ; Behavior, Animal/drug effects ; Cyclopropanes/administration & dosage/*pharmacology ; Disease Models, Animal ; Drug Synergism ; Drug Therapy, Combination ; Fibromyalgia/chemically induced/complications/*prevention & control ; Hydrogen-Ion Concentration ; Hyperalgesia/etiology/*prevention & control ; Injections, Intraperitoneal ; Male ; Pain/etiology/*prevention & control ; Pain Measurement ; Pain Threshold/*drug effects ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride ; Time Factors ; Tramadol/administration & dosage/*pharmacology