New Insights on Tramadol and Immunomodulation.

PURPOSE OF REVIEW: Opioids are administered to cancer patients although concerns have been raised that they may promote tumour growth or metastasis owing to their ability to suppress anti-cancer immunity. Tramadol has been reported to preserve or promote the immune response and may therefore be preferred to other opioids in cancer patients. We reviewed the literature documenting the immunomodulatory effects of tramadol. RECENT FINDINGS: Recent clinical evidence appears to confirm that tramadol possesses anti-inflammatory properties, and preserves some signalling cascades of the immune system relevant to anti-cancer defence. Tramadol is reported to promote or preserve immunity including natural killer cell activity which is important in anti-cancer defences.

Perforated peptic ulcer and short-term mortality among tramadol users.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is a strong risk and prognostic factor for peptic ulcer perforation, and alternative analgesics are needed for high-risk patients. * Pain management guidelines propose tramadol as a treatment option for mild-to-moderate pain in patients at high risk of gastrointestinal side-effects, including peptic ulcer disease. * Tramadol may mask symptoms of peptic ulcer complications, yet tramadol's effect on peptic ulcer prognosis is unknown. WHAT THIS STUDY ADDS: * In this population-based study of 1271 patients hospitalized with peptic ulcer perforation, tramadol appeared to increase mortality at least as much as NSAIDs. * Among users of tramadol, alone or in combination with NSAIDs, adjusted 30-day mortality rate ratios were 2.02 [95% confidence interval (CI) 1.17, 3.48] and 1.32 (95% CI 0.89, 1.95), compared with patients who used neither tramadol nor NSAIDs. AIM: Use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases risk and worsens prognosis for patients with complicated peptic ulcer disease. Therefore, patients who are at high risk of peptic ulcer often use tramadol instead of NSAIDs. Tramadol's effect on peptic ulcer prognosis is unknown. The aim was to examine mortality in the 30 days following hospitalization for perforated peptic ulcer among tramadol and NSAID users compared with non-users. METHODS: The study was based on data on reimbursed prescriptions and hospital discharge diagnoses for the 1993-2004 period, extracted from population-based healthcare databases. All patients with a first-time diagnosis of perforated peptic ulcer were identified, excluding those with previous ulcer diagnoses or antiulcer drug use. Cox regression was used to estimate 30-day mortality rate ratios for tramadol and NSAID users compared with non-users, adjusting for use of other drugs and comorbidity. RESULTS: Of 1271 patients with perforated peptic ulcers included in the study, 2.4% used tramadol only, 38.9% used NSAIDs and 7.9% used both. Thirty-day mortality was 28.7% overall and 48.4% among users of tramadol alone. Compared with the 645 patients who used neither tramadol nor NSAIDs, the adjusted mortality rate in the 30 days following hospitalization was 2.02-fold [95% confidence interval (CI) 1.17, 3.48] higher for the 31 'tramadol only' users, 1.41-fold (95% CI 1.12, 1.78) higher for the 495 NSAID users and 1.32-fold (95% CI 0.89, 1.95) higher for the 100 patients who used both drugs. CONCLUSION: Among patients hospitalized for perforated peptic ulcer, tramadol appears to increase mortality at a level comparable to NSAIDs.

Which has the least immunity depression during postoperative analgesia--morphine, tramadol, or tramadol with lornoxicam?

BACKGROUND: Analgesics are commonly used to provide pain relief after surgery. These drugs produce some extended depression of immunity. A prospective randomized controlled trial was designed to observe expressions of T-lymphocyte subsets (CD3(+), CD3(+)CD4(+) and CD3(+)CD8(+)), natural-killer cells (CD3(-)CD16(+)CD56(+)), and activated T-lymphocytes (CD3(+)CD25(+)) of patients undergoing gastric cancer surgeries and receiving patient-controlled intravenous analgesia (PCIA). METHODS: Forty-five patients undergoing elective gastric cancer surgeries under general anesthesia were randomly allocated into 3 groups. Group I received PCIA using morphine after surgery, group II using tramadol, and group III using tramadol with lornoxicam. The analgesic efficacy was evaluated by visual analog scale (VAS) and Bruggrmann comfort scale (BCS). Expressions of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD3(-)CD16(+)CD56(+), and CD3(+)CD25(+) were measured as percentages of total lymphocytes by flow cytometer at 5 time points. RESULTS: There was no significant difference in analgesic efficacy and the baselines of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD3(-)CD16(+)CD56(+), and CD3(+)CD25(+) in all groups. Compared with the baseline, CD3(+)CD8(+) had no changes in all groups at any time point. Ninety minutes after incision, CD3(+), CD3(+)CD4(+), CD3(-)CD16(+)CD56(+), and CD3(+)CD25(+) were lower in all groups (P<0.05). 24 h after surgery, CD3(+), CD3(+)CD4(+), CD3(-)CD16(+)CD56(+), and CD3(+)CD25(+) were lower in group I and group II (P<0.05); meanwhile CD3(+), CD3(+)CD4(+), and CD3(+)CD25(+) returned to the baseline but CD3(-)CD16(+)CD56(+) was still low (P<0.05) in group III. 48 h after surgery, CD3(+), CD3(+)CD4(+), CD3(-)CD16(+)CD56(+), and CD3(+)CD25(+) returned to the baseline in group II and group III, but not in group I (P<0.05). 72 h after surgery, CD3(+), CD3(+)CD4(+), CD3(+)CD4(+)/CD3(+)CD8(+) returned to the baseline, but CD3(+)CD25(+) and CD3(-)CD16(+)CD56(+) were still low in group I (P<0.05). CONCLUSION: PCIA using lornoxicam with tramadol has the same good analgesic efficacy and less immunity depression than PCIA using morphine or tramadol.