piperidines and Flushing

The use of remifentanil is often associated with the observation of mesenteric traction syndrome (MTS) soon after manipulation of the intestine during abdominal surgery. MTS symptoms include facial flushing, hypotension, and tachycardia. In the study reported here, we prospectively investigated the effects of remifentanil on the incidence of MTS in abdominal surgery.. One hundred patients scheduled for abdominal surgery were randomly assigned to two groups. In one group (n = 50), fentanyl alone was used as intravenous analgesic (control, group C); in the second group (n = 50), both fentanyl and remifentanil were used (remifentanil group, group R). In all patients, anesthesia was induced with propofol and rocuronium and then maintained with sevoflurane inhalation. Remifentanil was continuously infused for patients in group R as an analgesic. Plasma concentration of 6-keto-PGF(1α) was measured before surgery and 20 min after the skin incision was made in six patients of group R and seven patients of group C.. MTS occurred in 20 cases in group R (40.0%), but in only five cases in group C (10.0%). In both groups, the incidence of MTS was higher in laparotomy than in laparoscopic surgery. The plasma concentration of 6-keto-PGF(1α) was low in both groups before surgery and was elevated 20 min after skin incision in both groups in patients in whom MTS appeared.. The results of this study suggest that the use of remifentanil in laparotomy facilitates MTS.

Topics: 6-Ketoprostaglandin F1 alpha; Abdomen; Aged; Anesthesia Recovery Period; Anesthesia, General; Anesthetics, Intravenous; Flushing; Hemodynamics; Humans; Hypotension; Intraoperative Complications; Laparotomy; Mesentery; Middle Aged; Piperidines; Prospective Studies; Remifentanil; Splanchnic Circulation; Syndrome; Tachycardia

The use of niacin in the treatment of dyslipidemias is limited by the common side effect of cutaneous vasodilation, commonly termed flushing. Flushing is thought to be due to release of the vasodilatory prostanoids prostaglandin D2 (PGD2) and prostaglandin E2 from arachidonic acid metabolism through the cyclooxygenase pathway. Arachidonic acid is also metabolized by the cytochrome P450 system, which is regulated, in part, by the enzyme soluble epoxide hydrolase (sEH).. These experiments used an established murine model in which ear tissue perfusion was measured by laser Doppler to test the hypothesis that inhibition of sEH would limit niacin-induced flushing.. Niacin-induced flushing was reduced from 506 ± 126% to 213 ± 39% in sEH knockout animals. Pharmacologic treatment with 3 structurally distinct sEH inhibitors similarly reduced flushing in a dose-dependent manner, with maximal reduction to 143% ± 15% of baseline flow using a concentration of 1 mg/kg TPAU (1-trifluoromethoxyphenyl-3-(1-acetylpiperidin-4-yl) urea). Systemically administered PGD2 caused ear vasodilation, which was not changed by either pharmacologic sEH inhibition or sEH gene deletion.. Inhibition of sEH markedly reduces niacin-induced flushing in this model without an apparent effect on the response to PGD2. sEH inhibition may be a new therapeutic approach to limit flushing in humans.

Topics: Animals; Arachidonic Acid; Dinoprostone; Disease Models, Animal; Dose-Response Relationship, Drug; Epoxide Hydrolases; Flushing; Gene Deletion; Laser-Doppler Flowmetry; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Niacin; Phenylurea Compounds; Piperidines; Prostaglandin D2; Vasodilation; Vasodilator Agents

Topics: Antidepressive Agents; Flushing; Humans; Male; Middle Aged; Piperidines