Thoracic epidural administration has been shown to be beneficial, both with open and with endoscopic colorectal surgery.[32] Epidural blockade with local anesthetics improves postoperative ileus by blockage of inhibitory reflexes and efferent sympathetics. Studies have shown that combinations of thoracic epidurals containing bupivacaine alone or in combination with opioids improve postoperative ileus.[33, 34] Continuous intravenous administration of lidocaine during and after abdominal surgery may decrease the duration of postoperative ileus.[35]
In a randomized study, systemic infusion of lidocaine is compared with placebo infusions in postoperative patients. Patients in the lidocaine group appear to have earlier return of flatus, bowel function, and discharge to home. Although only 11 patients were used in the each arm, systemic lidocaine lessened the postoperative pain sensation. Therefore, it is recommended that further studies are warranted to evaluate systemic lidocaine infusion in postoperative patients.[36]
Peripherally selective opioid antagonists are an option for the treatment of postoperative ileus.[37] Methylnaltrexone (Relistor) and alvimopan (Entereg) are approved by the Food and Drug Administration. These agents inhibit peripheral mu-opioid receptors, which abolishes the adverse gastrointestinal effects of opioids; however, because these agents do not cross the blood-brain barrier, they do not impair the analgesic effects of opioids.[38]
Methylnaltrexone is indicated for opioid-induced constipation in patients with advanced illness receiving palliative care, when response to laxatives has not been sufficient. In a study of 14 healthy volunteers evaluating the use of morphine plus oral methylnaltrexone in increasing doses, methylnaltrexone significantly reduced morphine-induced delay in oral-cecal transit.[39] Another study reported subcutaneous methylnaltrexone is effective in inducing laxation in patients receiving palliative care who have opioid-induced constipation and in whom conventional laxatives have failed.[40] However, because methylnaltrexone has only recently been approved by the US Food and Drug Administration (FDA), more rigorous trials are needed.
Another phase III multicenter, double-blind, placebo-controlled study revealed that methylnaltrexone at 12-mg and 24-mg doses did not reduce the duration of postoperative ileus.[41] Although the utility of intravenous methylnaltrexone was not demonstrated, it was well tolerated by postcolectomy patients.[41]
Alvimopan is indicated to help prevent postoperative ileus following bowel resection. It has a longer duration of action than methylnaltrexone. Using data from four phase 3 bowel trials and one phase 4 radical cystemectomy trial, investigators evaluating the economic impact of postoperative adminstration of alvimopan (accounting for varying definitions of postoperative ileus) found that the addition of this agent to existing treatment strategies for those undergoing abdominal procedures resulted in overal hospital savings.[42]
Taguchi et al examined 78 postoperative patients randomized to receive either placebo or alvimopan.[43] Fifteen patients underwent partial colectomy, 36 were status post simple hysterectomy, and the remaining 27 underwent radical hysterectomy. All of the patients were on patient-controlled analgesia pumps using either meperidine or morphine. Compared with patients on placebo, patients on alvimopan had their first bowel movement 2 days earlier, resumed a solid diet 1.3 days earlier, and returned home 1.4 days earlier. Other recent trials have been completed, including a meta-analysis comparing alvimopan with placebo[44] and a study that found alvimopan to accelerate gastrointestinal tract recovery after bowel resection, regardless of age, gender, race, or concomitant medication.[45]
Use of prokinetic agents has shown mixed results. Randomized trials have shown some benefit of the colon-stimulating laxative bisacodyl for the treatment of ileus.[46, 47] Erythromycin, a motilin receptor agonist, has been used for postoperative gastric paresis but has not been shown to be beneficial for ileus.[48]Metoclopramide (Reglan), a dopaminergic antagonist, has antiemetic and prokinetic activities, but data have shown that the drug may actually worsen ileus. In a randomized controlled study on 210 patients undergoing major abdominal surgery, Wattchow et al reported that perioperative low dose celecoxib markedly reduced the development of paralytic ileus compared to diclofenac.[49] The effect was independent of narcotic use and was not associated with any increase in postoperative complications.
A review of meta-analyses and randomized controlled trials on drugs used for post-operative ileus was reported by Yeh et al.[50]The investigators identified three meta-analyses (2 on gum-chewing and 1 on alvimopan) and 18 clinical trials. Only gum chewing and alvimopan were effective in preventing ileus but due to safety concerns and costs with alvimopan, gum chewing may be preferred as first-line therapy. Gum chewing has also been used in women recovering from cesearian section with good effect when compared to standard of care in a randomized study conducted.[51]
In summary, ileus remains a significant health problem in North America. Successful therapy involves multimodality treatment such as minimally invasive/less traumatic surgery, opiate-sparing pain management, and fast tract recovery protocols.
http://emedicine.medscape.com/article/2242141-medication
