Opioid use by patients in an orthopedics spine clinic.Mahowald ML, Singh JA, Majeski P.Minneapolis VAMC, and the University of Minnesota, Minneapolis.OBJECTIVE: Concerns regarding the efficacy, toxicity, tolerance, dependence, and abuse of opioids have limited their use for patients with chronic spine pain. In our previous study of rheumatology clinic patients, opioid analgesics were found to be highly effective, produced only mild side effects, and had few instances of opioid abuse. The purpose of this study was to replicate our previous study in another large cohort of patients with nonmalignant pain due to well-defined spinal diseases. METHODS: Opioid use was studied in 230 orthopedics spine clinic patients by retrospective analysis of prescriptions for 3 years and cross-sectional analysis of efficacy and toxicity by patient interviews. Opioid use and stability of the daily dose over 3 years were derived from computerized pharmacy records. Medical records, operative reports, and radiographic studies were reviewed to determine the reason for dosage escalations and to detect instances of abuse or addiction behaviors. Patients were interviewed to determine the efficacy, frequency, and types of side effects and instances of obtaining opioids from sources outside the Veterans Affairs system. RESULTS: Opioids were prescribed for 152 of the 230 patients, for <3 months (short-term [STO]) in 94, >/=3 months (long-term [LTO]) in 58, and none in 72 (no opioid [NTO]). Medications prescribed were codeine, oxycodone, propoxyphene, Tramadol ( Generic Ultram ), morphine, meperidine, fentanyl, or hydroxycodone, either alone or in combination. Interviews were completed in 72 STO, 50 LTO, and 45 NTO patients. Pain severity (0-10 scale) was not different in patients with different spinal pathologies. Opioids significantly reduced the back pain severity score from 8.3 +/- 1.5 to 4.5 +/- 2.2 (mean +/- SD). Mild side effects (most commonly, constipation and sedation) were reported by 58% of the opioid-treated patients but rarely caused them to stop taking the medication. There was no significant increase from the mean +/- SD initial opioid dosage of 5.0 +/- 12.2 30-mg codeine equivalents per day (30 mg oral codeine = 5 mg oral morphine) to the mean peak dosage of 7.9 +/- 12.5 and the mean recent dosage of 4.3 +/- 6.3, suggesting that tolerance to opioid analgesia did not appear to occur in these patients. Dosage escalations of >2 30-mg codeine equivalents occurred 19 times in 17 LTO patients and was due to worsening of the underlying painful condition, complications of spine surgery, or unrelated surgical or medical problems in all but 3 of them (5%). These 3 patients also displayed other abuse behaviors. Abuse behaviors were not more frequent in those with or without a history of abuse/addiction. CONCLUSION: This study provides data on the efficacy, toxicity, tolerance, and abuse or addiction behaviors with opioid therapy in a large cohort of patients in an orthopedics spine clinic. The results provide objective data from patients with well-defined spine diagnoses to challenge the position that opioid treatment is inappropriate for chronic nonmalignant pain. This study provides clinical evidence to support and protect physicians treating patients with chronic musculoskeletal diseases, who may be reluctant to prescribe opioids because of possible sanctions from regulatory agencies. More important, it will benefit patients by permitting them to receive these effective, safe medications.

Sentinel node biopsy in melanoma of the trunk and the extremities in tumescent local anesthesia.

BACKGROUND. : The sentinel node biopsy (SNB) of axilla and groin is a common staging procedure and can be done in both general anesthesia and local anesthesia. OBJECTIVE. : To investigate the efficacy of tumescent local anesthesia (TLA) as a widely used type of local anesthesia in dermatologic surgery for the SNB of axilla and groin. METHOD. : From 1999 to 2002, 195 patients underwent a SNB of axilla or groin. A 0.1% tumescent solution with prilocaine was used. In cases in which local anesthesia did not produce complete analgesia, there was additional medication using Midazolam and Tramadol ( Generic Ultram ). RESULTS. : In 74.9% of the patients, TLA was sufficient as the sole method. In 25.1%, sedation became necessary. Additional medication was required for 31.9% of the patients with SNB in the axilla and for 17.3% with SNB in the groin; 26.6% of the patients with SNB of both axillas and 25% with SNB of the axilla and the groin received additional medication using Midazolam. Two patients with a SNB of the axilla received a combination of Midazolam and Tramadol ( Generic Ultram ). CONCLUSION. : SNB of the axilla and the groin in TLA is a good alternative to other anesthetic techniques, for example, general anesthesia or infiltration anesthesia.

Efficacy and safety of extended-release, once-daily Tramadol ( Generic Ultram ) in chronic pain: a randomized 12-week clinical trial in osteoarthritis of the knee.Babul N, Noveck R, Chipman H, Roth SH, Gana T, Albert K.TheraQuest, Blue Bell, Pennsylvania 19422, USA.The efficacy and safety of a once-daily extended-release formulation of Tramadol ( Generic Ultram ) hydrochloride (Tramadol ( Generic Ultram ) ER) was evaluated in patients with moderate to severe chronic pain of osteoarthritis (OA). This was a randomized, double-blind, placebo-controlled, parallel-group, 12-week study. Eligible patients with radiographically confirmed OA of the knee meeting the American College of Rheumatology diagnostic criteria, defined by knee pain and presence of osteophytes, plus at least age >50 years, morning stiffness <30 minutes in duration, and/or crepitus, entered a 2-7 day washout period during which all analgesics were discontinued. When pain at the index knee joint reached > or =40 mm (0-100 mm VAS), patients were randomized to Tramadol ( Generic Ultram ) ER or placebo. Tramadol ( Generic Ultram ) ER was initiated at 100 mg QD and increased to 200 mg QD by the end of 1 week of treatment. After the first week, further increases to Tramadol ( Generic Ultram ) ER 300 mg or 400 mg QD were allowed. Outcome measures included arthritis Pain Intensity Visual Analogue Scale (VAS), Western Ontario and McMaster Universities arthritis Scale (WOMAC) Pain, Stiffness, Physical Function VAS subscales, Patient and Physician Global Assessment of Therapy, Sleep, dropouts due to insufficient therapeutic effect, and adverse events. Two hundred forty-six patients were randomized (Tramadol ( Generic Ultram ) ER 124, placebo 122). There were no baseline differences between the two treatments. The mean age was 61 years, mean duration of OA 12.9 years, and the mean Tramadol ( Generic Ultram ) ER dose was 276 mg QD. All efficacy outcome measures favored Tramadol ( Generic Ultram ) ER over placebo. On the primary outcome variable of average change from baseline in arthritis Pain Intensity VAS over 12 weeks, Tramadol ( Generic Ultram ) ER was superior to placebo (least squares mean change from baseline: 30.4 mm vs. 17.7 mm, P < 0.001). Significant differences from placebo were evident at week 1, the first post-treatment visit. Similarly, outcomes on the WOMAC Pain, Stiffness and Physical Function subscales, the WOMAC Composite Scale, dropouts due to insufficient therapeutic effect, Patient and Physician Global Assessment of Therapy, and Sleep were all significantly better with Tramadol ( Generic Ultram ) ER than placebo (P < 0.001 to < 0.05). Treatment with Tramadol ( Generic Ultram ) ER results in statistically significant and clinically important and sustained improvements in pain, stiffness, physical function, global status, and sleep in patients with chronic pain. A once-a-day formulation of Tramadol ( Generic Ultram ) has the potential to provide patients increased control over the management of their pain, fewer interruptions in sleep and improved compliance.

Microencapsulation and characterization of Tramadol ( Generic Ultram )-resin complexes.

A rapid and reliable analytical method is described for the simultaneous determination of RWJ-38705 (Tramadol ( Generic Ultram ) N-oxide) and several of its major metabolites in the plasma of Sprague-Dawley rats and Beagle dogs. Sample preparation using solid phase extraction was followed by reversed phase liquid chromatography (LC) coupled with tandem mass spectrometric (MS/MS) detection in the positive ionization mode. The assay was linear for all analytes over concentrations ranging from approximately 6 to 2000 ng/ml. The inter-assay reproducibility was generally less than 15% while accuracy values were within 13% of theoretical. The overall recovery of the analytes ranged from approximately 40 to 64% in rat plasma and 53-75% in dog plasma. This assay has proven to be sensitive, specific and reproducible, and it has been readily implemented in preclinical PK studies. Representative plasma concentration versus time profiles resulting from administration of TNO to rats and dogs are presented in this communication.

Patient-controlled analgesia (PCA) for postoperative pain relief. A prospective observational study for evaluating the technology in a ward routine

Patient-controlled analgesia (PCA) is rarely used on surgical wards despite described advantages of this method as compared to conventional techniques. Uncertainties in patient selection and insufficient evaluation of this technique may explain these circumstances. The aim of our study was to evaluate PCA on general surgery and traumatology wards by means of standardized criteria for technology assessment (i.e. safety, practicability, benefit for patients and medical staff) and the efficacy of pain relief. In a prospective study we investigated 120 patients. In phase I, we performed analgesic therapy with Tramadol ( Generic Ultram )/metamizol (50 ASA status I-IV patients). In phase II, piritramid had been applied to 70 ASA status I-II patients after an intermediate analysis of phase I. In 7% of the patients technical problems led to an early interruption even at the end of the study period. There were, however, no incidents which caused vital problems for the patients. A mean postoperative pain level of 55 visual analogue scale points (0-100 point scale) was achieved with Tramadol ( Generic Ultram )/metamizol. PCA was stopped in 16% of the patients due to the occurrence of nausea or vomiting and in two patients due to insufficient pain relief. The use of piritramid in phase II led to lower pain levels and no interruptions of PCA because of ineffectivity or nausea/vomiting.

The effect of concentration of hydrophilic (hydroxypropyl methylcellulose [HPMC]) and hydrophobic polymers (hydrogenated castor oil [HCO], ethylcellulose) on the release rate of Tramadol ( Generic Ultram ). Hydrophilic matrix tablets were prepared by wet granulation technique, while hydrophobic (wax) matrix tablets were prepared by melt granulation technique and in vitro dissolution studies were performed using United States Pharmacopeia (USP) apparatus type II. Hydrophobic matrix tablets resulted in sustained in vitro drug release (>20 hours) as compared with hydrophilic matrix tablets (<14 hours). The presence of ethylcellulose in either of the matrix systems prolonged the release rate of the drug. Tablets prepared by combination of hydrophilic and hydrophobic polymers failed to prolong the drug release beyond 12 hours. The effect of ethylcellulose coating (Surelease) and the presence of lactose and HPMC in the coating composition on the drug release was also investigated. Hydrophobic matrix tablets prepared using HCO were found to be best suited for modulating the delivery of the highly water-soluble drug, Tramadol ( Generic Ultram ) hydrochloride.
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AIM: To compare the pharmacokinetics of the enantiomers of trans-Tramadol ( Generic Ultram ) (trans-T) and its active metabolite, trans-O-demethylTramadol ( Generic Ultram ) (M1), in male and female rats. METHODS: Following a single oral dose of 10 mg/kg trans-T hydrochloride to rats, (+)-trans-T, (-)-trans-T, (+)-M1, and (-)-M1 in plasma were determined by a high performance capillary electrophoresis method. RESULTS: The females showed higher plasma concentrations of (+)-trans-T, (-)-trans-T, and (+)-M1 than the males. The enantiomers of trans-T were absorbed and eliminated more slowly in the females than in the males. (+)-M1 was eliminated more slowly in the females than in the males. All pharmacokinetic parameters but Tmax of the two enantiomers of trans-T were significantly different in both sex rats. The (+)/(-)-enantiomeric ratios of the pharmacokinetic parameters for trans-T in the males were similar to those in the females. The values of Cmax, AUC(0-infinity) of the two enantiomers of M1 were significantly different in both sex rats. The (+)/(-)-enantiomeric ratios of Cmax, AUC(0-infinity) for M1 were lower than 1 in the males, larger than 1 in the females. CONCLUSIONS: Systemic exposure of (+)-trans-T, (-)-trans-T, and (+)-M1 was higher in female rats than in male rats. The stereoselectivity in pharmacokinetics of trans-T was similar, and that of M1 was different in male and female rats.