Alvimopan, a peripherally acting mu-opioid receptor antagonist, compared with placebo in postoperative ileus after major abdominal surgery: results of a randomized, double-blind, controlled study. Does pantothenic acid accelerate the return of bowel motility in post-operative patients? Negative effect of Metoclopramide in postoperative adynamic ileus. A prospective, randomized, double blind study. Cisapride in the treatment of post-operative ileus. Effect of combined blockade of beta-adrenoceptors and acetylcholinesterase in the treatment of postoperative ileus after cholecystectomy. Treatment of postoperative paralytic ileus with cisapride. Treatment of postoperative paralytic ileus by intravenous lidocaine infusion. Comparison of the effects of thoracic epidural analgesia and i.v. infusion with lidocaine on cytokine response, postoperative pain and bowel function in patients undergoing colonic surgery. [Evaluation of the use of caerulein (ceruletide) in the postoperative of abdominal surgery]. Cisapride does not reduce postoperative paralytic ileus. Double-blind study of the treatment of the adynamic ileus with fructose-1,6-diphosphate. A double-blind, randomized, placebo-controlled phase III study of the safety of alvimopan in patients who undergo simple total abdominal hysterectomy. Effect of intravenous erythromycin on postoperative ileus. Intravenous lidocaine speeds the return of bowel function, decreases postoperative pain, and shortens hospital stay in patients undergoing radical retropubic prostatectomy. The evolution of postoperative ileus after laparoscopic cholecystectomy. A comparative study with conventional cholecystectomy and sympathetic blockade treatment. Treatment of postoperative ileus after bowel surgery with low-dose intravenous erythromycin. Modulation of the adrenergic system in the treatment of postoperative bowel atonia. Usefulness of caerulein in the treatment of post-operative intestinal atony. Phase III trial of alvimopan, a novel, peripherally acting, mu opioid antagonist, for postoperative ileus after major abdominal surgery. Lack of effect of metoclopramide on colonic motility after cholecystectomy. Small bowel motility following major intra-abdominal surgery: the effects of opiates and rectal cisapride. Effect of cisapride on distal colonic motility in the early postoperative period following left colonic anastomosis. A prospective, randomized, double-blinded, placebo-controlled trial of cisapride after colorectal surgery. Beta-adrenoceptor blockade in the treatment of postoperative adynamic ileus. Pharmacological manipulation of adynamic ileus: controlled randomized double-blind study of ceruletide on intestinal motor activity after elective abdominal surgery. The effect of cholecystokinin on postoperative bowel function. [Postoperative intestinal atony and vasopressin. A randomized study of the effect of administration of vasopressin on the duration of postoperative intestinal atony]. [A double-blind study of neostigmine versus placebo in paralytic ileus as a result of surgical interventions]. Prokinetic effect of erythromycin after colorectal surgery: randomized, placebo-controlled, double-blind study. Alvimopan, a novel, peripherally acting mu opioid antagonist: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial of major abdominal surgery and postoperative ileus. The effect of erythromycin on bile excretion and proximal small bowel motility following divided gastric bypass surgery: a prospective randomized placebo-controlled trial. Effects of propranolol on human postoperative ileus. Does metoclopramide reduce the length of ileus after colorectal surgery? A prospective randomized trial. Selective postoperative inhibition of gastrointestinal opioid receptors. Oncotic pressure, albumin and ileus: the effect of albumin replacement on postoperative ileus. Dihydroergotamine in postoperative ileus.
Alvimopan is a peripherally acting mu-opioid receptor (PAM-OR) antagonist for accelerating gastrointestinal recovery after surgery.
                Patients undergoing open laparotomy (bowel resection, n = 418; hysterectomy, n = 197) were randomized to receive alvimopan 6 or 12 mg or placebo orally > or = 2 h before surgery and then b.i.d. until hospital discharge (up to 7 days). The primary efficacy endpoint was time to gastrointestinal (GI) recovery (measured by toleration of solid food and passage of flatus/stool; GI-3). Secondary endpoints included time to GI-2 recovery (toleration of solid food and passage of stool) and hospital discharge order written (DCO).
                Alvimopan did not significantly accelerate GI-3 compared with placebo [6 mg: hazard ratio (HR) = 1.20, p = 0.080; 12 mg: HR = 1.24, p = 0.038). However, after adjustment for significant covariates (sex/surgical duration), benefits were significant for both doses (6 mg: HR = 1.24, p = 0.037; 12 mg: HR = 1.26, p = 0.028). Alvimopan also significantly accelerated time to GI-2 (6 mg: HR = 1.37, p = 0.008; 12 mg: HR = 1.33, p = 0.018) and DCO (6 mg: HR = 1.31, p = 0.008; 12 mg: HR = 1.28, p = 0.015). Adverse events were similar between groups.
                Alvimopan (6 or 12 mg) accelerates GI recovery and is well tolerated in patients undergoing open laparotomy. nan In a double blind controlled study including 60 patients it was found that Metoclopramide has a negative effect upon the resolution of postoperative adynamic ileus. Metoclopramide causes a delay in the time from operation to the first passage of flatus. The effect of cisapride on duration of post-operative ileus after surgery was investigated in a randomized, double-blind, placebo-controlled study. Patients undergoing elective upper gastrointestinal (n = 47) or colonic (n = 22) surgery were pre-operatively randomly allocated to treatment with either cisapride 30 mg t.d.s., by rectal administration, or placebo. Treatment started exactly 48 h after surgery if the patient at this time had not passed stool. Time to passage of first stool after surgery was estimated. Mean time to passage of stool was 85 (32) h (s.d.) for cisapride-treated and 91 (43) h for placebo-treated patients. No difference between the treatment groups was noted. Treatment with cisapride did not shorten the duration of postoperative ileus after either upper gastrointestinal or colonic surgery. The effect of treatment with a non-selective beta-adrenoceptor blocker (propranolol) and an acetylcholinesterase blocker (neostigmine) on the duration of postoperative ileus after cholecystectomy was investigated in a double-blind, randomized study comprising 51 patients. Propranolol (P), 10 mg intravenously twice daily was, together with neostigmine (N), 0.5 mg subcutaneously twice daily, administered to 16 patients. Eighteen patients were treated with neostigmine, 0.5 mg subcutaneously twice daily only, and 17 patients were placebo-treated controls (C). The medical treatment started in the evening of the day of operation. The time to first passage of stool after operation was determined and used as a measure of duration of the postoperative ileus. The mean time was 68 +/- 6 h in the P + N-treated group, 82 +/- 6 h in the N group, and 90 +/- 7 h in the C group. The difference between the P + N group and controls was significant (p less than 0.01). P + N was effective in patients older than 60 years (p less than 0.01), whereas no effect was seen in patients younger than 60 years. In conclusion, treatment with a combination of propranolol and neostigmine shortened the duration of postoperative paralytic ileus after cholecystectomy. This effect was not seen after treatment with neostigmine only. The effect of P + N was most marked in patients older than 60 years. The effect of cisapride on postoperative colonic motility was studied in 40 patients undergoing cholecystectomy under randomized, double-blind conditions. The patients received 10 mg of cisapride or placebo by intravenous injection starting on the day of surgery and repeated every 12 h until the 3rd postoperative day. The return of propagative motility in the colon was visualized by means of radiopaque markers and serial abdominal radiographs. Cisapride induced a significantly earlier return of propulsive motility in the right colon, as indicated by the propagation of markers from the ascending colon to the transverse colon (p less than 0.05). Radiopaque markers reached the descending colon (p less than 0.05) and the rectosigmoid colon (p less than 0.05) significantly earlier in the cisapride group than in controls. The first passage of feces occurred significantly earlier in cisapride-treated patients than in controls (p less than 0.05). The first passage of gas after surgery did not differ significantly between the groups. Our results suggest that cisapride can be used to induce earlier return of propagative motility in the colon after major abdominal surgery. The effects of continuous intravenous infusion of lidocaine on postoperative paralytic ileus in cholecystectomized patients was investigated in this double-blind study. An infusion of lidocaine (3 mg/min, n = 15) or an infusion of an equal volume of saline (n = 15) was started 30 min before induction of anesthesia and continued for 24 h after surgery. Postoperative colonic motility was evaluated by radiopaque markers and serial abdominal radiographs. A record was kept of the first passage of gas and feces. Results showed significantly earlier return of propulsive motility in the colon of lidocaine-treated patients. Radiopaque markers in the lidocaine group were propelled significantly earlier from the cecum/ascending colon to the transverse colon (P less than 0.05) and appeared significantly earlier in the descending colon (P less than 0.05) and the rectosigmoid colon (P less than 0.05) than in saline-treated patients. Despite the fact that the mean time for postoperative defecation occurred 17 h earlier in lidocaine-treated patients, differences between the groups were not statistically significant--a fact due, perhaps, to great individual variations in defecation habits. The time to first passage of gas, a variable representative of changes in anorectal or colonic tone rather than propagative motility, also did not differ significantly between the groups. No adverse reactions to lidocaine were reported. The results suggest that continuous intravenous infusion of lidocaine during the first postoperative day shortens the duration of paralytic ileus in the colon after abdominal surgery. Suppression of inhibitory gastrointestinal reflexes by reduction of postoperative peritoneal irritation is suggested as the mechanism of action. Both thoracic epidural analgesia (TEA) and i.v. lidocaine were able to decrease postoperative pain and duration of ileus. We compared TEA and i.v. lidocaine (IV) regarding their effects on cytokines, pain and bowel function after colonic surgery.
                Sixty patients were randomly allocated to one of the three groups. TEA group had lidocaine 2 mg kg(-1) followed by 3 mg kg(-1) h(-1) epidurally and an equal volume of i.v. normal saline. The IV group received the same amount of lidocaine i.v. and normal saline epidurally. The control group received normal saline via both routes. These regimens were started 30 min before surgery and were continued throughout. Blood cytokines were measured at scheduled times within 72 h.
                Both TEA and IV groups had better pain relief. The total consumptions using patient-controlled epidural analgesia were 81.6 (6.5), 55.0 (5.3) and 45.6 (3.9) ml (P<0.01) and the times of flatus passage were 50.2 (4.9), 60.2 (5.8) and 71.7 (4.7) h (P<0.01) in the TEA, IV and control groups, respectively. The TEA group exhibited the best postoperative pain relief and the least cytokine surge. The IV group experienced better pain relief and less cytokine release than the control group.
                The TEA lidocaine had better pain relief, lower opioid consumption, earlier return of bowel function and lesser production of cytokines than IV lidocaine during 72 h after colonic surgery; IV group was better than the control group. In order to evaluate the efficacy of Caerulein in the postoperative stage of abdominal surgery, 25 patients received 0.3 mcg/kg intravenously every 4 hours. Bowel Movements, passage of gases, first evacuation and general improvement were compared to 25 patients in similar conditions who didn't receive the drug. The study group showed an earlier appearance of intestinal motility as compared to the control group. This contributed in a relevant matter to an earlier discharge from the hospital. The differences with the control group were statistically significative. The benefits of the drug in the management of the postoperative stage of abdominal surgery are discussed. nan nan The purpose of this study was to investigate the safety and efficacy of alvimopan, a novel peripherally acting mu-opioid receptor antagonist, in patients who undergo simple total abdominal hysterectomy.
                Women (n = 519) were randomized (4:1) to receive alvimopan 12 mg (n = 413) or placebo (n = 106) > or = 2 hours before the operation then twice daily for 7 days (hospital and home). Adverse events were monitored up to 30 days after the last dose of study drug was administered. Efficacy was assessed for 7 postoperative days.
                Overall, the most common adverse events were nausea, vomiting, and constipation; < 5% of patients discontinued use because of adverse events. Alvimopan significantly accelerated the time to first bowel movement (hazard ratio, 2.33; P <.001). Average time to first bowel movement was reduced by 22 hours, with more frequent bowel movement and better bowel movement quality found in the treatment cohort.
                Alvimopan has a safety profile that is similar to that of placebo and provides significantly improved lower gastrointestinal recovery in women who undergo simple total abdominal hysterectomy. We attempted to determine whether the administration of erythromycin shortens the period of postoperative ileus by a prospective, double-blind, placebo-controlled study. Seventy-seven patients were randomized and included in the statistical calculations. The patients were stratified according to the operation performed (cholecystectomy, celiotomy, or other major abdominal operations). Forty-one patients (group 1) received 250 mg erythromycin intravenously every 8 h for nine doses upon admission to the recovery room. Thirty-six patients (group 2) received placebo. The time (in hours) to first passage of flatus, first liquid meal, first bowel movement, and total length of hospital stay was recorded. There was no significant difference between group 1 and group 2 in time to first flatus (54.9 +/- 29 vs. 53.9 +/- 27 h, respectively), first meal (70.4 +/- 44 vs. 71.7 +/- 65), first bowel movement (81.8 +/- 32 vs. 80.1 +/- 28), or length of hospital stay (185.2 +/- 183 vs. 182.1 +/- 163). Erythromycin, in the dosage tested in this study, does not seem to alter clinical parameters of gastrointestinal motility after an abdominal operation. New prokinetic agents may deserve further studies. Postoperative ileus is a concern among surgical patients. Epidural anesthesia and analgesia with local anesthetics can decrease the duration of ileus. Significant systemic absorption of local anesthesia occurs during epidural use. In this study, we examined whether many of the beneficial effects on bowel function seen with epidural lidocaine are also present when the drug is given parenterally. Forty patients undergoing radical retropubic prostatectomy were studied with one half of the patients receiving a lidocaine bolus (1.5 mg/kg) and infusion (3 mg/min, unless weight <70 kg, then 2 mg/min); the other half received a saline infusion. A blind observer recorded the patient's daily pain score, the time the patient first experienced flatulence and had the first bowel movement, and the total use of analgesics. Lidocaine-treated patients first experienced flatulence in a significantly shorter time (P < 0.01) than control patients. Lidocaine patients' hospital stay was also significantly shorter (P < 0.05); on average, they spent 1.1 fewer days in the hospital. I.V. lidocaine initiated before anesthesia and continued 1 h postoperatively significantly sped up the return of bowel function. Lidocaine patients were also more comfortable postoperatively. Many of the bowel function benefits attributed to epidural lidocaine are also present when the drug is administered parenterally. Additionally, the length of hospital stay was reduced in lidocaine-treated patients. Implications: This study prospectively examined whether I.V. lidocaine could affect the return of bowel function after radical prostate surgery. Lidocaine-treated patients had shorter hospital stays, less pain, and faster return of bowel function. In this population, lidocaine infusion can be a useful adjunct in anesthetic management. Our study is prompted by the arrival of laparoscopic cholecystectomy in connection with the evolution of postoperative ileus (PI) and by its avoidance of the intraabdominal handling implied in conventional cholecystectomy. With this aim a prospective, controlled, randomized, and blind clinical trial was designed using 100 patients divided into five groups (n = 20): I, conventional cholecystectomy (CC): II, CC+injection of 20 ml bupivacaine 0.5% into the mesentery root; III, CC + 7.5 mg propranolol i.v. and 0.5 mg neostigmine s.c., postoperatively until the first defecation; IV, II+III; and V, laparoscopic cholecystectomy. The shortest period of PI was observed in group V. This period increases notably in group IV (53 h), group II (72 h), and group III (84 h) relative to the control group with (89 h). This reduction in PI time runs parallel with an improvement in the patient's general state of well-being. We concluded that after laparoscopic cholecystectomy PI is nonexistent. Furthermore, this study confirms the correlation between the avoidance of intraabdominal manipulation and the evolution of postoperative ileus. Treatment of postoperative ileus remains unsatisfactory. Erythromycin (EM), a macrolide antibiotic, has prokinetic effects on the gut. We investigated whether intravenous erythromycin decreases the time to the return of normal bowel function after bowel surgery in patients with bladder cancer and interstitial cystitis who have undergone cystectomy and urinary diversion.
                We conducted a double-blind, randomized, placebo-controlled study of 22 volunteers. On the first postoperative day, patients began receiving intravenous erythromycin (125 mg) or placebo every 8 hours (maximum of 21 doses). The patients' ability to tolerate a general diet and return of bowel function was monitored.
                A general diet was tolerated at a median of 9 days postoperatively for the EM arm and 8 for the placebo arm (P = 0.60). The first bowel sounds were detected at an average of 2 postoperative days for the EM arm and 3 for the placebo arm (P = 0.88). First flatus was present an average of 5 days postoperatively for both study arms (P = 0.35). The first bowel movement was present an average of 6 days postoperatively for the EM arm and 5 for the placebo arm (P = 0.98).
                No significant difference was found between EM and placebo with regard to the onset of bowel sounds, passage of flatus, passage of the first bowel movement, and the time to tolerate a general diet. These data indicate that erythromycin is not useful in improving postoperative bowel function. Sympathetic hyperactivity is considered to be the most important factor in the development of postoperative bowel atonia. In a double-blind study we evaluated the gut motor effects of dihydroergotamine, which predominantly acts as a sympatholytic agent in the gastrointestinal tract. Forty-six patients undergoing cholecystectomy received either 0.5 mg dihydroergotamine + 5000 U heparin or 5000 U heparin alone (controls) twice daily in a randomized order starting on the morning of the operation. The first postoperative bowel movement occurred 57 +/- 4 h (means +/- SEM) after operation in the patients receiving dihydroergotamine, compared with 102 +/- 4 h in the control patients (p less than 0.001). Electromyography performed in the stomach and upper small bowel on the 3rd postoperative day showed an increase in the number of activity fronts of the interdigestive migrating motor complex and in the duration of spike activity under the influence of dihydroergotamine compared with the controls (p less than 0.001). It is concluded that dihydroergotamine stimulates depressed gut motility after abdominal surgery and that sympatholysis is the likely mechanism of action. We conducted a controlled clinical trial designed to test caerulein for tolerability and effectiveness in post-operative patients recovering from abdominal surgery. The test product was administered 24 hours after surgery, by intravenous drip infusion, at the rate of 2 nanograms/kg/minute. The results were compared with parallel observations made in a matched group of patients receiving no drugs or manipulation likely to promote intestinal peristalsis with the exception of the application of a nasogastric tube for aspiration and the water and electrolyte replenishment customary in the post-operative period. The results of this study evince a clear-cut difference between the two groups of patients in regard to the restoration of intestinal peristalsis and the passing of flatus and faeces, as confirmed by statistical analysis (Cochran's test) demonstrating the significant (p less than 0.01) superiority of caerulein treatment relative to the untreated control group. Likewise, the study revealed the excellent tolerability of the test drug at the dosage employed. Postoperative ileus presents significant clinical challenges that potentially prolong hospital stay, contribute to readmission, and increase morbidity. There is no approved treatment for postoperative ileus. Alvimopan is a novel, peripherally acting, mu opioid receptor antagonist currently in development for the management of postoperative ileus.
                Patients undergoing partial colectomy or simple or radical hysterectomy were randomized to receive alvimopan 6 mg (n = 152), alvimopan 12 mg (n = 146), or placebo (n = 153) orally 2 hours before surgery and twice daily thereafter until discharge or for up to seven days. The primary efficacy end point, time to return of gastrointestinal function, was a composite measure of passage of flatus or stool and tolerating solid food. Secondary end points included time to the hospital discharge order written. Adverse events were monitored throughout the study.
                Mean time to gastrointestinal recovery was significantly reduced in patients treated with alvimopan 6 mg vs. placebo (hazard ratio = 1.45; P = 0.003), with a smaller reduction seen with alvimopan 12 mg (hazard ratio = 1.28; P = 0.059). Mean time to the hospital discharge order written was significantly accelerated in patients treated with alvimopan 6 mg (hazard ratio = 1.50; P < 0.001). The most common treatment-emergent adverse events across all treatment groups were nausea, vomiting, and hypotension; the incidence of nausea and vomiting was reduced by 53 percent in the alvimopan 12-mg group.
                In patients undergoing major abdominal surgery, alvimopan accelerated gastrointestinal recovery and time to the hospital discharge order written compared with placebo and was well tolerated. The effect of metoclopramide on postoperative colonic ileus was evaluated in a randomised, double-blind study in 20 patients after cholecystectomy. The start of propulsive colonic motility and colonic transit time after operation were measured by radio-opaque markers and serial abdominal radiographs. Metoclopramide 20 mg given intravenously three times a day until the fourth postoperative day (n = 10) did not significantly reduce the duration of postoperative colonic paralysis compared with control patients (n = 10), nor were there any differences between the groups when the time of first postoperative passage of gas and faeces were compared. In conclusion, the use of metoclopramide in the postoperative period did not result in a quicker return of propulsive motility in the right or left colon as judged by the radio-opaque markers and serial abdominal radiographs. Human small bowel motility is altered after laparotomy. Opiate analgesia is a possible cause of these alterations, and cisapride is a potential therapy.
                Continuous proximal small bowel manometry was performed for up to 92 hours in 23 patients after major intra-abdominal surgery. They were treated with rectal cisapride (30 mg three times daily) or placebo until the clinical resolution of ileus. Small bowel manometry was performed for 30 hours in 5 volunteers receiving 1 mg/kg meperidine over 3 hours.
                Phase III activity was present within 3 hours of the end of surgery in all patients. Initially, the migrating motor complex (MMC) period was markedly reduced (mean, 22 minutes) but gradually increased. Phase II activity was absent until a median of 40 hours had elapsed. Phase III contractile amplitude was markedly attenuated in the jejunum, in contrast to that in the duodenum, presumably as a result of dilatation and/or altered tone, increasing to normal by 72 hours. In the volunteer group, although the MMC period was reduced by meperidine, it remained significantly greater than that of the placebo patient group for approximately 48 hours and phase II was reduced but not eliminated. Cisapride induced some changes in motor activity but did not accelerate the recovery of normal motility. Clinical outcome, assessed by the return of bowel sounds and passage of flatus, was accelerated by cisapride, but the trend was not significant (P = 0.11).
                This is the first published study using prolonged manometry to show the gradual evolution of small bowel motor activity after major intra-abdominal surgery. The findings suggest that surgery decreases the MMC period to the equivalent of the absolute refractory period, thereby eliminating phase II, which returns as the MMC period lengthens. Cisapride, at the dosage given, confers only modest benefit. This study was designed to investigate the modulatory effect of cisapride on colonic motility in the postoperative period.
                A prospective, double-blind, randomized, placebo-controlled trial of 14 patients undergoing left colonic anastomosis was carried out. Manometric probes were positioned with transducers on either side of the anastomosis, and colonic activity was recorded continuously for a median of 98 (range, 72-144) hours using an ambulatory system. Quantitative indices of motility were calculated with an automated analysis program.
                Isolated waveform activity returned at a median of 1.8 (interquartile range, 1-3) hours and motor complex activity at 24 (interquartile range, 19-30) hours in the placebo group and at similar times in the cisapride group. All motility variables except mean amplitude increased significantly with time in both groups. In the cisapride group the motility index was significantly increased compared with the placebo group (P = 0.03), resulting from an increase in percentage duration of activity (P = 0.002). Activity index, mean amplitude of waveforms, and number of waves greater than 50 cm H2O did not differ between groups. In contrast to placebo, cisapride significantly increased the median number of waves greater than 13 cm H2O and percentage duration of activity distal to the anastomosis compared with proximally. The return of bowel sounds (median, 43, interquartile range, 24-48 hours vs. 67, 29-69 hours; P = 0.2) or first passage of flatus (78, 54-94 hours vs. 94, 81-105 hours; P = 0.1) did not differ between groups.
                Although cisapride may have a differential effect on the colon proximal and distal to an anastomosis and significantly increases some indices of motility in the early postoperative period, these are unlikely to be of any clinical relevance. The predominant factor prolonging hospitalization and delaying oral intake after colorectal surgery continues to be return of large bowel function. We investigated the effect of the cisapride on postoperative bowel motility.
                Patients were started on cisapride versus a placebo on postoperative day 1 after colorectal surgery. Endpoints included the time to patients' first bowel movement, time of advancement to regular diet, time of hospitalization, and cost analysis. Results were analyzed using a Mann-Whitney test.
                Thirty-five patients were entered in the study, consisting of 17 in the cisapride group and 18 in the placebo group. The median time to first bowel movement, advancement of diet, and hospital discharge was 1 day less in the cisapride group compared with the placebo group (P <0.05). There was a substantial cost savings in the study group.
                Cisapride use results in statistically significant improvement in postoperative bowel motility. Cisapride should be added as adjunct treatment in postoperative care after colorectal surgery. Abdominal trauma, such as surgery and peritonitis, leads to inhibition of intestinal motility, partly mediated by alpha- and beta-adrenoceptors. To investigate the effect of nonselective beta-blockade on adynamic ileus, propranolol was compared with placebo in the postoperative course after elective colonic surgery in a double-blind randomized study. Ten patients received 4 mg propranolol intravenously twice daily, and ten received 10 mg intravenously twice daily. Nineteen patients received placebo. The time to first passage of stool was 110 +/- 9 h in the placebo group and 82 +/- 11 h in the 4-mg propranolol group. In the 10-mg propranolol group, the time was 79 +/- 8 h. The difference between the placebo-treated group and the propranolol-treated groups was significant (p less than 0.01). The effect of propranolol was most marked in older patients and after surgery on the distal colon. In patients older than 60 years the time to first stool in the placebo group was 127 +/- 13 h (n = 8), compared with 73 +/- 8 h (n = 11) in the propranolol group (p less than 0.01). In patients who had undergone surgery on the distal colon the time to first stool was 125 +/- 13 h (n = 8) in the placebo group and 76 +/- 8 h (n = 11) for propranolol (p less than 0.01). Adverse effects on the respiratory or cardiovascular system were not seen during medication. It is concluded that propranolol shortens the period of adynamic ileus after colonic surgery. In a double-blind placebo-controlled trial of patients undergoing elective abdominal surgery (n = 91), a single intravenous infusion of ceruletide (2.5 ng kg-1 min-1 for 1 hour) resulted in audible bowel sounds in 42/47 patients as opposed to 30/44 receiving placebo (P less than 0.025). Excessive bowel sounds were noted in 16 patients in the ceruletide group and four receiving placebo (P less than 0.01). Significantly more patients (P less than 0.01) in the ceruletide group (22/45 versus 9/44) passed flatus per rectum between the second and third post-operative day. Ceruletide infusion was accompanied by a significant increase in the incidence of nausea and vomiting (P less than 0.005, P less than 0.0025) but these side effects were short-lived. These results indicate that ceruletide is likely to be a useful therapeutic agent for acute intestinal adynamic motility disorders. Cholecystokinin (CCK) was used in a randomized double-blind trial to evaluate its effect on post-operative paralytic ileus. Sixty patients were admitted to the study. The return of postoperative intestinal motility was registered with subjective and/or objective methods. No differences were found between the CCK group and the placebo group. nan A fully randomized double-blind study, stratified according to diagnosis, was carried out in order to assess the effect of endonasal neostigmine in the treatment of post-laparotic paralytic ileus. A total of 40 patients (16 M, 24 F), aged between 22 and 76 years old, were admitted to the study; of these 20 were cholecystectomized and 20 had undergone emergency surgery. According to a special randomization list, 10 patients from each pathological group were treated with 6% neostigmine en (1 puff = 5.4 mg) and the other ten were treated with placebo. Both treatments were administered at a dose of 2 puffs, one per nostril, at the end of surgery and then repeated every 4 hours up to a maximum of 6 puffs/day. Treatment was continued for 4 days or until canalization of feces and gas was achieved. The mean daily dose of endonasal neostigmine found to be efficacious was 4 puffs/day, equivalent to 24.7 mg in cholecystectomized patients and 23.5 mg in patients undergoing emergency surgery. In over-all terms the canalization of gas and feces was observed in 74% of patients treated with neostigmine and in 45% of those receiving placebo and the difference was statistically significant. Nausea and vomiting three to seven days after an elective operation on the colon and rectum remain a persistent clinical problem. Erythromycin, a safe, inexpensive drug that stimulates intestinal motilin receptors, has previously been shown to accelerate gastric emptying significantly after upper gastrointestinal surgery. We aimed to evaluate the effect of postoperative intravenous erythromycin on postoperative ileus in patients undergoing elective surgery for primary colorectal cancer.
                Between May 1998 and April 1999, 150 patients undergoing primary resection of colon or rectal cancer were enrolled in this prospective, randomized, placebo-controlled trial. One hundred thirty-four patients completed the study. Patients were excluded if they had extensive metastatic disease, were taking medications known to interact with erythromycin, or if they required an ileostomy. Patients received either 200 mg of intravenous erythromycin or placebo every six hours. Clinical endpoints were recorded and continuous end-points are presented as mean +/- standard deviation.
                There were no significant complications related to erythromycin. The erythromycin (n = 65) and placebo (n = 69) groups were comparable regarding demographic and operative factors. The erythromycin group had a slightly shorter length of time to passage of flatus (4.1 +/- 1.3 vs. 4.4 +/- 1.1 days; P = 0.03). There was no significant difference between erythromycin and placebo in time to first solid food (5.6 +/- 1.9 vs. 5.4 +/- 1.8 days), time to first bowel movement (5.2 +/- 1.9 vs. 5.4 +/- 1.3 days), or time to discharge from hospital (7.5 +/- 2.0 vs. 7.6 +/- 2.8 days). There was no difference in the rate of clinically significant nausea (26 vs. 26 percent; P = 0.99), vomiting (17 vs. 16 percent; P = 0.88), or nasogastric tube placement (9 vs. 7 percent; P = 0.68).
                Erythromycin does not seem to alter clinically important outcomes related to postoperative ileus in patients undergoing resection for colorectal cancer. To demonstrate that alvimopan (6 or 12 mg) accelerates recovery of gastrointestinal (GI) function in patients undergoing laparotomy for bowel resection or radical hysterectomy.
                Postoperative ileus (POI) following laparotomy may increase morbidity and extend hospitalization. Opioids can contribute to the duration of POI. Alvimopan is a novel opioid receptor antagonist in development for the management of POI.
                A total of 510 patients scheduled for bowel resection or radical hysterectomy were randomized (1:1:1) to receive alvimopan 6 mg, alvimopan 12 mg, or placebo orally > or =2 hours before surgery, then twice a day (b.i.d.) until hospital discharge or for up to 7 days. The primary efficacy end point was a composite of time to recovery of upper and lower GI function. An associated secondary end point was time to hospital discharge order written.
                The modified intent-to-treat population included 469 patients (451 bowel resection and 18 radical hysterectomy patients). Time to recovery of GI function was accelerated for the alvimopan 6 mg (hazard ratio [HR] = 1.28; P < 0.05) and 12 mg (HR = 1.54; P < 0.001) groups with a mean difference of 15 and 22 hours, respectively, compared with placebo. The time to hospital discharge order written was also accelerated in the alvimopan 12 mg group (HR = 1.42; P = 0.003) with a mean difference of 20 hours compared with placebo. The incidence of adverse events was similar among treatment groups.
                Alvimopan accelerated GI recovery and time to hospital discharge order written compared with placebo in patients undergoing laparotomy and was well tolerated. No conclusive data exists supporting the use of any prokinetic agent in the postoperative setting. The study was designed to examine the effect of erythromycin on small bowel motility in a placebo-controlled trial of post gastric bypass patients utilizing a standardized nuclear medicine test.
                A consecutive series of 21 patients undergoing elective gastric bypass surgery for morbid obesity between September 1999 and March 2001 were enrolled in this prospective double-blind randomized controlled trial. Standard open, divided gastric bypass was performed. Patients were randomized to receive either erythromycin 250 mg i. v. (11 patients) or placebo (10 patients) every 8 hours. On postoperative day 2, a hepatic iminodiacetic acid (HIDA) scan was obtained. Tracer movement through the biliary tree and proximal small bowel was quantified and compared.
                Tracer clearance from the liver and biliary tree was no different between groups from time of injection through 1 hour. Tracer material clearance from the duodenum into the jejunum was no different between the erythromycin and control groups at 1 hour, 37% +/- 13% and 37% +/- 22% respectively (P = 0.95). At 4 hours, clearance was greater in the erythromycin group, 77% +/- 6%, compared to control, 60% +/- 20% (P = 0.036). The rate of tracer change between hour 1 and 4 (slope) was steeper in the erythromycin group (P = 0.048).
                Erythromycin increases intestinal transit in the postoperative setting. The sympathetic nervous hyperactivity present in response to surgical stress has been implicated as an important component of the postoperative paralytic ileus. A randomized and prospective study was conducted, evaluating the effects of the preoperative beta-adrenergic blockade with propranolol in schistosomotic patients during the period of postoperative ileus.
                The study compared schistosomotic patients submitted, or not, to beta-adrenergic blockade. Basal cardiac frequency was determined and propranolol was used in a dose of 40 mg twice a day. The dose was adjusted weekly until a minimum decrease of 20% in cardiac frequency was achieved. Three coupled bipolar electrodes were placed in the left colon in both groups, and registration of myoelectric activity of the left colon was made twice a day during the period of postoperative ileus using a system of data collection (DATA Q Series 200). The electric signals were previously amplified, filtered and separated into Electric Control Activity (ECA) and Electric Response Activity (ERA).
                The dose of propranolol varied from 80 to 160 mg/day. The proportional decrease in basal heart frequency varied from 20 to 33%, with an average of 25.4 +/- 3.9% in the propranolol group, maintaining a mean of 24.3 +/- 3.6% decrease in the postoperative period. Differences on clinical recovery of the postoperative ileus were not found. Significant differences on electromyographic patterns were not observed between the groups, except for the presence of a greater number of short-duration contractions in the second postoperative day in the beta-blocked group.
                The authors suggest that the preoperative beta-adrenergic blockade with propranolol does not determine myoelectric activity changes that could contribute to an earlier resolution of postoperative ileus.
                Copyright 2001 S. Karger AG, Basel Between August 1988 and September 1989, 100 consecutive patients who underwent elective abdominal colorectal surgical procedures were prospectively randomized to receive or not to receive metoclopramide. Metoclopramide was intravenously administered every 8 hours from the completion of surgery until a solid food diet was able to be tolerated. Seven patients were not included in the final tabulations because of one death, one small bowel obstruction requiring laparotomy, one anastomotic leak requiring laparotomy, and four protocol violations. Ninety-three patients, 37 men and 56 women (mean age, 59.5; range, 14-89 years) underwent 40 segmental colectomies, 13 total abdominal colectomies, 8 abdominoperineal resections, 8 ileoanal pouch procedures, 7 small bowel resections, and 17 other colorectal procedures. The 40 patients who received postoperative metoclopramide were in Group 1, and the 53 who did not were in Group 2. The mean length of time between laparotomy and commencement of oral fluid and oral solid intake in Groups 1 and 2 were 3.5 and 4.8 days, and 3.5 and 5.0 days, respectively. These differences were not statistically significant (P greater than 0.05). Prolonged ileus was seen in seven patients in Group 1 and in eight patients in Group 2. These differences were also not statistically significant (P greater than 0.05). Prolonged ileus was defined as the need for nasogastric tube reinsertion or discontinuation of oral intake. We conclude that metoclopramide does not significantly alter the course of postoperative ileus. Postoperative recovery of gastrointestinal function and resumption of oral intake are critical determinants of the length of hospital stay. Although opioids are effective treatments for postoperative pain, they contribute to the delayed recovery of gastrointestinal function.
                We studied the effects of ADL 8-2698, an investigational opioid antagonist with limited oral absorption that does not readily cross the blood-brain barrier, on postoperative gastrointestinal function and the length of hospitalization. We randomly assigned 79 patients--including 1 whose surgery was canceled--to receive one capsule containing 1 mg or 6 mg of ADL 8-2698 or an identical-appearing placebo capsule two hours before major abdominal surgery and then twice daily until the first bowel movement or until discharge from the hospital. Data were analyzed for 26 patients in each of the three groups; all received opioids for postoperative pain relief. Observers who were unaware of the group assignments evaluated the outcomes.
                Fifteen patients underwent partial colectomy and 63 underwent total abdominal hysterectomy. Patients given 6 mg of ADL 8-2698 had significantly faster recovery of gastrointestinal function than those given placebo. The median time to the first passage of flatus decreased from 70 to 49 hours (P=0.03), the median time to the first bowel movement decreased from 111 to 70 hours (P=0.01), and the median time until patients were ready for discharge decreased from 91 to 68 hours (P=0.03). Effects in the group that received 1 mg of ADL 8-2698 were less pronounced.
                Selective inhibition of gastrointestinal opioid receptors by an antagonist with limited oral absorption that does not readily cross the blood-brain barrier speeds recovery of bowel function and shortens the duration of hospitalization. The effect of decreased colloid oncotic pressure, as seen in hypoalbuminemia and hypoproteinemia, upon intestinal function has been well delineated in the surgical literature. Patients undergoing abdominal aortic aneurysm resection or aortoiliac or aortofemoral bypass grafts are almost uniformly hypoalbuminemic postoperatively; with these two facts in mind, a prospective, randomized clinical study was undertaken to identify the role of serum albumin concentration on the length of postoperative ileus in this population. The main hypothesis was that patients whose albumin levels dropped below 3.5 gm/dL would have a more prolonged postoperative hospital course as a result of delay in return of bowel function when compared with those patients in whom the low albumin levels were exogenously acutely replenished to > 3.5 gm/dL. Albumin was replaced to a level greater-than or equal to 3.5 g/dL in one group of 37 patients (AR), with a control group of 32 patients (NR) not receiving any albumin. Return of bowel function was measured by the postoperative day that flatus was documented, as well as the postoperative day oral intake was resumed. Mean values were determined for each group, and t tests did not reveal a significant difference in postoperative day of flatus (AR mean = 4.06 days, NR mean = 4.16 days) or postoperative day of oral intake (AR mean = 4.0, NR mean = 3.75). Additional comparisons between the groups involving the number of postoperative days until a regular diet was begun (AR mean = 6.06, NR mean = 5.48) and length of postoperative hospital stay (AR mean = 9.16, NR mean = 8.43) failed to reveal significant differences.(ABSTRACT TRUNCATED AT 250 WORDS) The effects of dihydroergotamine (DHE) on postoperative ileus after major abdominal surgery were studied. Forty-one patients received 0.5 mg DHE subcutaneously twice a day from the day of surgery to the seventh postoperative day. Thirty-three patients served as controls. There were no significant differences in the time to the first postoperative passage of flatus or delivery of stools nor in the quantity of laxatives given. It is concluded that DHE does not reduce the duration of postoperative ileus.
Alvimopan may prove to be beneficial but proper judgement needs adherence to reporting standards. Further trials are needed on intravenous lidocaine and neostigmine. The remaining drugs can not be recommended due to lack of evidence or absence of effect.