Salsalate, morphine, and postoperative ileus

Background Previously, we demonstrated that ketorolac, a nonsteroidal antilnflammatory drug (NSAID), prevented postoperative small bowel ileus in a rodent model. The aim of this study was to evaluate the effect of salsalate, an NSAID without antlplatelet effect, on postoperative ileus alone or in combination with morphine. Methods Forty-eight rats underwent placement of duodenal catheters and were then randomly assigned to one of eight groups (n = 6). Four groups had standardized laparotomy following drug administration, whereas 4 groups underwent the same treatment without laparotomy: control and morphine animals received 0.1 mL alcohol via the catheter, whereas salsalate and salsalate-plus-morphine animals received salsalate (15 mg/kg) dissolved in 0.1 mL alcohol. The animals also received 0.5 mg/kg morphine (morphine and salsalate plus morphine) or the same volume of saline (control and salsalate) subcutaneously. Transit was measured following the injection of a nonabsorbed marker via the duodenal catheter and is defined as the geometric center (GC) of distribution. An additional 20 rats had serosal electrodes placed on the jejunum, and were assigned to one of four treatment groups (control, salsalate, morphine, and salsalate plus morphine; n = 5 each group). Myoelectric activity was recorded until the reappearance of the migrating myoelectric complex (MMC) following laparotomy. Results Laparotomy and morphine independently reduced small bowel transit (P = 0.0006 and 0.006, respectively, by three-way analysis of variance [ANOVA]; GC 4.3 ± 0.2 control versus 2.2 ± 0.3 laparotomy versus 3.6 ± 0.4 morphine), but morphine did not further worsen postoperative transit (GC 2.4 ± 0.4; P = 0.42). Although salsalate did not alter baseline transit, pretreatment improved postoperative transit (P = 0.0002; GC 3.6 ± 0.4). This effect was lost with the addition of morphine (GC 2.7 ± 0.2; P = 0.21). The MMCs returned earlier after laparotomy in salsalate-pretreated rats (63 ± 18 minutes salsalate versus 160 ±12 minutes laparotomy; P<0.01, one-way ANOVA). However, this effect was also lost in animals receiving morphine (106 ± 16 min; P>0.05). Conclusion Salsalate improves postoperative small bowel motility in a rodent model; however, this effect is masked by morphine.