The Effects of Tramadol and Fentanyl on Gastrointestinal Motility in Septic Rats Ismet Topcu, N. Zeynep Ekici, Rusen Isik, and Melek Sakarya Department of Anesthesiology and Intensive Care, Celal Bayar University, Manisa, Turkey In this study, we investigated the effects of tramadol and fentanyl on gastrointestinal transit (GIT) during acute systemic inflammation in an experimental model of cecal ligation and perforation (CLP). One-hundred- twenty male Swiss-Albino rats were divided randomly into 6 groups: Group I = sham-operated + saline; Group II = sham-operated + fentanyl; Group III = sham-operated + tramadol; Group IV = CLP + saline; Group V = CLP + fentanyl; Group VI = CLP + tram- adol. Suspension of charcoal was administered as an intragastric meal to measure the GIT. GIT% (mean  sd) were 46.1%  9.8%, 43.2%  9.8%, 45.9%  10.2%, 33.2%  9.2%, 24.9%  4.1%, and 31.8%  8.4% in Groups I, II, III, IV, V, and VI, respectively. GIT% was significantly less in Group V than in Groups I, II, III, and IV (P  0.05). The Group VI mean value was signifi- cantly lower than those of Groups I, II, and III (P  0.05) but not different from those of Groups IV and V (P  0.05). The antitransit effect of fentanyl was shown to have increased in the experimental sepsis model, but no decrease in GIT was obtained with tramadol. This was thought to be the result of an associated endogenic opi- oid system activation and receptor upregulation in sepsis. (Anesth Analg 2006;102:876 –81) E ndogenous opioid peptide (EOP) and opioid recep- tors (OR) are widespread in the mammalian gas- trointestinal tract (1,2). EOPs are present in neuro- nal cell bodies and nerve fibers of the myenteric and submucosal plexus, antral G cells, and enterochromaffin cells in the gut (1). Physiologic roles of the endogenous opioid system (EOS) most probably include the inhibi- tory control of motility, inhibition of secretion, and the modulation of mechanoreceptor sensitivity in the gut (1,2). Furthermore, it has been verified that tissue injury and peripheral inflammation induce a local increase in EOP and a sensitization or upregulation of OR (3). A comparison of inflammatory and noninflammatory tis- sues demonstrated that the antinociceptive effect is def- initely increased in the presence of inflammation be- cause of peripheral opioid effects (3,4). EOS may increase the incidence of duodenogastric reflux, vomiting, and pulmonary aspiration as a result of its inhibitory effect on gastric emptying and intes- tinal motility (5). Furthermore, EOS decreases biliary, pancreatic, and intestinal secretions and delays intes- tinal motility (6,7). This is especially important in sep- tic patients, who are unable to tolerate absorptive dysfunction or motility disturbances that can accom- pany enteral nutrition. Consequently, duodenogastric reflux, colonization with enteric Gram-negative patho- gens, or translocation may occur (8,9). Because of the adverse effects of opioids on the gastrointestinal tract, alternative analgesic drugs that do not have significant effects on gastrointestinal mo- tility may offer advantages, especially for patients with sepsis. Tramadol, a synthetic analog of codeine, is a cen- trally acting analgesic with a low affinity for -opioid receptors. This affinity of tramadol at -opioid recep- tors is some 6000 times less than that of morphine (10). Tramadol also modifies pain transmission by inhibit- ing neuronal noradrenaline and serotonin reuptake and by stimulating serotonin release (11,12). Tramadol has an analgesic potency similar to that of meperidine, but it is associated with less respiratory depression than conventional opioids (10). The present study was designed to determine the effects of the -opioid agonist fentanyl and the atyp- ical analgesic tramadol on gastrointestinal transit (GIT) during acute systemic inflammation in an exper- imental model caused by surgical cecal ligation and perforation (CLP). Methods All rats procedures were approved by the Committee on the Humane Care of Laboratory Animals of the Accepted for publication October 17, 2005. Address correspondence and reprint requests to Ismet Topcu, MD, Guzelyurt Mah. Ingolstadt Cad., Anadolu Konutlari No:11, 45030 Manisa, Turkey. Address e-mail to topcuismet@yahoo.com. DOI: 10.1213/01.ane.0000196506.28780.94 ©2006 by the International Anesthesia Research Society 876 Anesth Analg 2006;102:876–81 0003-2999/06