The serotonin syndrome is a potential side-effect of serotonin-enhancing drugs, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs). We recently reported a genetic mouse model for the serotonin syndrome, as serotonin transporter (SERT)-deficient mice have exaggerated serotonin syndrome behavioural responses to the MAOI tranylcypromine and the serotonin precursor 5-hydroxy-l-tryptophan (5-HTP). As numerous case reports implicate the atypical opioids tramadol and meperidine in the development of the human serotonin syndrome, we examined tramadol and meperidine as possible causative drugs in the rodent model of the serotonin syndrome in SERT wild-type (+/+), heterozygous (+/−) and knockout (−/−) mice. Comparisons were made with SERT mice treated with either vehicle or morphine, an opioid not implicated in the serotonin syndrome in humans. Here we show that tramadol and meperidine, but not morphine, induce serotonin syndrome-like behaviours in mice, and we show that this response is exaggerated in mice lacking one or two copies of SERT. The exaggerated response to tramadol in SERT−/− mice was blocked by pretreatment with the 5-HT1A antagonist WAY 100635. Further, we show that morphine-, meperidine- and tramadol-induced analgesia is markedly decreased in SERT−/− mice. These studies suggest that caution seems warranted in prescribing or not warning patients receiving SSRIs or MAOIs that dangerous side-effects may occur during concurrent use of tramadol and similar agents. These findings suggest that it is conceivable that there might be increased vulnerability in individuals with SERT polymorphisms that may reduce SERT by more than 50%, the level in SERT+/− mice.

Summary

Background and objective: This placebo-controlled study was performed to evaluate the efficacy of dexmedetomidine compared with meperidine and placebo in preventing postanaesthetic shivering. Methods: We studied 120 patients (ASA I–II) scheduled for elective abdominal or orthopaedic surgery of about 1–3 h duration. Forty patients in each group randomly received 1 μg kg−1 of dexmedetomidine, 0.5 mg kg−1 of meperidine or saline 0.9% as placebo, intravenously (i.v.). Mean arterial pressure, heart rate, oxygen saturation and central body temperature were measured. Extubation, awakening and orientation times, shivering, pain, recovery and sedation scores were recorded. Results: Postanaesthetic shivering was seen in 22 patients in the placebo group, four patients in the meperidine group and six patients in the dexmedetomidine group. Sedation scores were significantly higher in the dexmedetomidine group compared with meperidine and placebo groups. Both dexmedetomidine and meperidine caused a significantly prolonged extubation and awakening time compared with placebo. Also, dexmedetomidine caused a significantly prolonged orientation time compared with other two groups. Conclusion: Intraoperative intravenously administration of dexmedetomidine 1 μg kg−1 reduces postanaesthetic shivering as does meperidine 0.5 mg kg−1 in patients after major surgery.

Background and objective: Comparison of the effectiveness of tramadol with meperidine given intravenously to emergency patients with suspected renal colic.

Methods: A double-blind, randomized clinical trial was performed in the Emergency Department of a tertiary-care university hospital. Consecutive patients with suspected renal colic (n =47) were randomized to receive intravenously an initial dose of tramadol 50 mg (n = 23) or meperidine 50 mg (n = 24). After 30 min, additional doses of meperidine 50 mg were given intravenously as a rescue medication in an open fashion. Pain relief was assessed using a 10 cm visual analogue scale, the primary outcomes being pain relief at 15 and 30 min after the analgesics. Secondary outcomes were the frequency of rescue meperidine use and the development of side-effects.

Results: Visual analogue scale pain scores after 15 and 30 min decreased in both tramadol and meperidine groups (P < 0.05). However, pain relief was better in the meperidine group at the 15 and 30 min evaluations (P < 0.05). Only 11 patients (48%), initially receiving meperidine, needed more meperidine compared with 16 patients (67%) initially receiving tramadol. Both drugs were well tolerated with no adverse effects occurring in either group.

Conclusions: Meperidine 50 mg was superior to tramadol 50 mg for acute pain relief in patients with suspected renal colic when given intravenously. Because many patients in both groups received supplemental meperidine and the response to tramadol alone cannot be predicted, clinicians may want to choose higher doses of meperidine alone or other alternative combinations.