piperidines and Intestinal-Pseudo-Obstruction

Postoperative ileus is common and is a major clinical problem. It has been widely studied in patients and in experimental models in laboratory animals. A wide variety of treatments have been tested to prevent or modify the course of this disorder.. This review draws together information on animal studies of ileus with studies on human patients. It summarizes some of the conceptual advances made in understanding the mechanisms that underlie paralytic ileus. The treatments that have been tested in human subjects (both pharmacological and non-pharmacological) and their efficacy are summarized and graded consistent with current clinical guidelines. The review is not intended to provide a comprehensive overview of ileus, but rather a general understanding of the major clinical problems associated with it, how animal models have been useful to elucidate key mechanisms and, finally, some perspectives from both scientists and clinicians as to how we may move forward with this debilitating yet common condition.

Topics: Anesthesia, Epidural; Animals; Benzofurans; Chewing Gum; Cholinergic Agents; Contrast Media; Cyclooxygenase Inhibitors; Diatrizoate Meglumine; Digestive System Surgical Procedures; Enhanced Recovery After Surgery; Enteral Nutrition; Enteric Nervous System; Fluid Therapy; Gastrointestinal Agents; Gastrointestinal Motility; Ghrelin; Humans; Ileus; Inflammation; Intestinal Pseudo-Obstruction; Intubation, Gastrointestinal; Laparoscopy; Mast Cells; Piperidines; Postoperative Complications; Serotonin 5-HT4 Receptor Agonists; Sympathetic Nervous System; Sympatholytics

Alvimopan (ADL 8-2698; Adolor Corporation, Exton, PA, USA) is a novel, peripherally restricted opioid antagonist. After oral administration, it has activity specific to the gastrointestinal (GI) tract. ADL 8-2698 has low systemic absorption and a high affinity for mu-opioid receptors. In healthy subjects, ADL 8-2698 antagonized loperamide-induced changes in GI transit and prevented morphine-induced delays in oral-cecal transit time without antagonizing centrally mediated opioid effects, such as analgesia or pupillary constriction. In the treatment of opioid naive patients who underwent surgery and received opioids for acute pain, oral ADL 8-2698 (6.0 mg) improved the management of postoperative ileus (POI) by shortening the time to achieve normal bowel function and, ultimately, hospital stay. Postoperative nausea and vomiting and the overall incidence of all GI side effects were reduced in patients treated with ADL 8-2698 for POI. Analgesia was not compromised, because there were no changes in median opioid consumption or Visual Analog Scale (VAS) pain scores in patients treated with ADL 8-2698 versus patients treated with placebo. No drug-related side effects were observed in acute pain postsurgical patients in the initial POI study. In patients treated with opioids for chronic pain or opioid addiction, lower doses of oral ADL 8-2698 (0.5 to 3.0 mg) reversed opioid bowel dysfunction (OBD) and normalized GI activity. These effects were evident without compromising opioid analgesia or inducing central nervous system symptoms of withdrawal. Some chronic opioid patients receiving apparently supramaximal doses of ADL 8-2698 (> or = 3.0 mg) reported localized GI side effects, possibly indicative of a localized GI withdrawal response. The most common side effects of ADL 8-2698 in chronic pain patients with OBD were abdominal pain, flatulence, and diarrhea. These effects were not observed in most OBD patients receiving lower doses of ADL 8-2698. Overall, ADL 8-2698 was well tolerated in clinical trials. Further studies to evaluate the efficacy and safety of ADL 8-2698 in clinical practice are in progress.

Topics: Analgesia; Analgesics, Opioid; Animals; Gastrointestinal Transit; Humans; Intestinal Pseudo-Obstruction; Intestines; Narcotic Antagonists; Pain Measurement; Piperidines; Postoperative Complications

Topics: Adult; Animals; Child; Cisapride; Constipation; Esophageal Motility Disorders; Gastrointestinal Diseases; Gastrointestinal Motility; Gastroparesis; Humans; Infant; Intestinal Pseudo-Obstruction; Piperidines

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Cisapride; Female; Gastrointestinal Motility; Humans; Infant; Intestinal Pseudo-Obstruction; Male; Middle Aged; Piperidines; Randomized Controlled Trials as Topic; Serotonin Antagonists

Topics: Cisapride; Constipation; Dyspepsia; Esophagitis; Esophagus; Forecasting; Gastric Emptying; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Hydrogen-Ion Concentration; Intestinal Pseudo-Obstruction; Intestines; Manometry; Piperidines; Serotonin Antagonists; Stomach

Topics: Anemia, Pernicious; Anorexia Nervosa; Cisapride; Connective Tissue Diseases; Diabetes Complications; Domperidone; Drug-Related Side Effects and Adverse Reactions; Gastric Emptying; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Intestinal Pseudo-Obstruction; Metoclopramide; Piperidines; Postgastrectomy Syndromes; Stomach Diseases

Alvimopan (ADL 8-2698; Adolor Corporation, Exton, PA, USA) is a novel, peripherally restricted opioid antagonist. After oral administration, it has activity specific to the gastrointestinal (GI) tract. ADL 8-2698 has low systemic absorption and a high affinity for mu-opioid receptors. In healthy subjects, ADL 8-2698 antagonized loperamide-induced changes in GI transit and prevented morphine-induced delays in oral-cecal transit time without antagonizing centrally mediated opioid effects, such as analgesia or pupillary constriction. In the treatment of opioid naive patients who underwent surgery and received opioids for acute pain, oral ADL 8-2698 (6.0 mg) improved the management of postoperative ileus (POI) by shortening the time to achieve normal bowel function and, ultimately, hospital stay. Postoperative nausea and vomiting and the overall incidence of all GI side effects were reduced in patients treated with ADL 8-2698 for POI. Analgesia was not compromised, because there were no changes in median opioid consumption or Visual Analog Scale (VAS) pain scores in patients treated with ADL 8-2698 versus patients treated with placebo. No drug-related side effects were observed in acute pain postsurgical patients in the initial POI study. In patients treated with opioids for chronic pain or opioid addiction, lower doses of oral ADL 8-2698 (0.5 to 3.0 mg) reversed opioid bowel dysfunction (OBD) and normalized GI activity. These effects were evident without compromising opioid analgesia or inducing central nervous system symptoms of withdrawal. Some chronic opioid patients receiving apparently supramaximal doses of ADL 8-2698 (> or = 3.0 mg) reported localized GI side effects, possibly indicative of a localized GI withdrawal response. The most common side effects of ADL 8-2698 in chronic pain patients with OBD were abdominal pain, flatulence, and diarrhea. These effects were not observed in most OBD patients receiving lower doses of ADL 8-2698. Overall, ADL 8-2698 was well tolerated in clinical trials. Further studies to evaluate the efficacy and safety of ADL 8-2698 in clinical practice are in progress.

Topics: Analgesia; Analgesics, Opioid; Animals; Gastrointestinal Transit; Humans; Intestinal Pseudo-Obstruction; Intestines; Narcotic Antagonists; Pain Measurement; Piperidines; Postoperative Complications

We assessed upper gastrointestinal anatomy and function with contrast radiology and antroduodenal manometry in 51 children with chronic intestinal pseudo-obstruction (CIP) prior to entering these patients into an open-label outpatient trial of cisapride. The diagnosis of CIP was based on characteristic symptoms requiring special nutritional support (parenteral in 30, tube feeding in 12) or interfering with daily activities (documented by diary in nine). At a time the subjects were not acutely ill, antroduodenal pressures were recorded for > 4 h fasting and > 1 h after a complex liquid meal. Results were categorized by the most prominent manometric abnormality as myopathy (n = 6), absent migrating motor complex (MMC) (n = 27), failure to induce fed pattern (n = 7), MMC plus discrete abnormalities (n = 7), and postprandial duodenal hypomotility (n = 4). Patients in the first two categories did not have effective MMCs, but those in the last three categories did. Compared to children without MMCs, those with MMCs rarely required parenteral nutrition (p < 0.001). All children were treated with oral cisapride 0.2 mg/kg/dose t.i.d., and evaluated every 2 months for up to 1 yr. Of 49 evaluable subjects, the final global assessment was unchanged in 25, fair (improved symptom score) in 17, or excellent (change from TPN to tube feeding or tube feeding to oral feeding) in seven. Children with MMCs (13 of 18) responded more often to cisapride than those without MMCs (11 of 31), p < 0.02. All four subjects with postprandial duodenal hypomotility had excellent responses. Children with normal diameter bowel responded more often than those with dilated bowel, p < 0.004. To summarize, in children with CIP, absence of the MMC was associated with need for greater intensity of nutritional support and decreased response rate to cisapride. The response to cisapride was highly variable within the study group, but often could be predicted by the presence or absence of bowel dilation and MMCs.

Topics: Child, Preschool; Chronic Disease; Cisapride; Enteral Nutrition; Female; Humans; Intestinal Pseudo-Obstruction; Linear Models; Male; Manometry; Myoelectric Complex, Migrating; Parenteral Nutrition, Total; Piperidines; Serotonin Antagonists

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.

Topics: Cholecystectomy; Cisapride; Colonic Diseases; Double-Blind Method; Female; Gastrointestinal Motility; Humans; Intestinal Pseudo-Obstruction; Male; Middle Aged; Piperidines; Postoperative Complications; Serotonin Antagonists

To assess the effect of cisapride on gastrointestinal motility and gastric emptying in children with chronic intestinal pseudoobstruction, 20 children (mean age, 4.9 years; 14 female and 6 male) who required special means of alimentation or who had severe symptoms confirmed by diary during 2 weeks before the study were studied. A motility catheter with recording sites in the antrum and duodenum was placed on the first day of the study and remained in place until the end of the 5-day study. Cisapride (0.3 mg/kg PO t.i.d.) or placebo was given in double-blind randomized crossover fashion, with a 2-day "washout" interval. Antroduodenal motility was recorded on days 2 and 5. Recording consisted of 4 hours of fasting and 2 hours after a complex liquid meal labeled with 99mTc. Gastric emptying was assessed for 1 hour after the meal. Based on manometry, 16 patients had neuropathic and 4 patients had myopathic disorders. Cisapride had no effect on the discrete, qualitative abnormalities found in individual records. Cisapride increased the postprandial duodenal motility index from 1180 +/- 256 mm Hg/30 min after placebo to 2385 +/- 430 mm Hg/30 min (P less than 0.05) but had no significant effect on the antral motility index. Cisapride did not alter the profound delay in gastric emptying; time to reach 50% of initial activity (T1/2) was 105 +/- 20 vs. 93 +/- 19 minutes and percentage of retention after 60 minutes (R60) 56% +/- 4% vs. 58% +/- 4% in control vs. cisapride, respectively. In summary, in children with chronic intestinal pseudoobstruction, cisapride increased postprandial duodenal motility but did not improve gastric emptying.

Topics: Child; Child, Preschool; Cisapride; Double-Blind Method; Duodenum; Eating; Female; Gastric Emptying; Gastrointestinal Motility; Humans; Infant; Intestinal Pseudo-Obstruction; Male; Manometry; Piperidines; Serotonin Antagonists

We conducted a 12-month trial of cisapride (10 mg three times a day) in 21 patients with gastric stasis due to clinically and manometrically diagnosed gastroparesis (N = 9; seven due to diabetes) or chronic intestinal pseudo-obstruction (N = 12). Radionuclide solid-liquid gastric emptying tests were performed at baseline and at the end of the 12-month period. Symptoms were assessed monthly by diary and every three months by the investigators; frequency and severity of symptoms were scored in a standardized manner. For the whole group of 21 patients, gastric emptying of both solids and liquids improved significantly after one year of cisapride (P less than 0.05). Among chronic intestinal pseudoobstruction patients, there was predominantly an improvement in gastric emptying of solids; in contrast, patients with gastroparesis had a greater improvement in liquid emptying. Total symptom score improved significantly in the gastroparesis group (median score: 8 at baseline vs 6 at one year, P less than 0.05) but not in the chronic intestinal pseudoobstruction patients (median score at baseline 10 vs 9 at one year). Similarly, body weight showed a trend towards improvement in the gastroparesis group. No significant side effects were noted. We conclude that during a 12-month open trial, cisapride was effective in improving gastric emptying in patients with gastric stasis and consistently improved symptoms in those with gastroparesis.

Topics: Administration, Oral; Adult; Body Weight; Chronic Disease; Cisapride; Double-Blind Method; Female; Gastric Emptying; Humans; Intestinal Pseudo-Obstruction; Male; Piperidines; Serotonin Antagonists; Stomach Diseases

Topics: Cisapride; Clinical Trials as Topic; Constipation; Dyspepsia; Gastroesophageal Reflux; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Intestinal Pseudo-Obstruction; Piperidines; Serotonin Antagonists; Stomach Ulcer

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Cisapride; Female; Gastrointestinal Motility; Humans; Infant; Intestinal Pseudo-Obstruction; Male; Middle Aged; Piperidines; Randomized Controlled Trials as Topic; Serotonin Antagonists

We have investigated the effect of oral cisapride (10 mg t.i.d.) in a double-blind, placebo-controlled trial in 26 patients with upper gut dysmotility: 11 with gastroparesis (8 diabetic, 3 idiopathic) and 15 with chronic idiopathic intestinal pseudoobstruction. Patients were evaluated at entry and at the end of the 6-wk study by upper gastrointestinal manometry, scintigraphic evaluation of gastric emptying of solids and liquids, measurement of body weight, and scoring of the following symptoms: abdominal pain, nausea, vomiting, early satiety, bloating, and distention. Cisapride and placebo groups were strictly comparable for all parameters assessed. Cisapride resulted in a significant increase in the gastric emptying of solids (p less than 0.05) compared with placebo; cisapride also tended to increase the postcibal antral motility and normalize the abnormal manometric features in the patients with intestinal dysmotility, particularly the characteristics of fasting interdigestive motor complexes and the fed motor pattern. Both cisapride and placebo groups showed an improvement in total symptom scores and there was no significant difference in overall symptom response between the two groups. However, the change in abdominal pain was greater with cisapride (p = 0.07). Cisapride facilitates gastric emptying in patients with upper gut dysmotility. The overall symptomatic benefit during a 6-wk trial of cisapride, 10 mg t.i.d., was not greater than that of placebo, and dose-response as well as longer term trials are necessary to determine the clinical efficacy of this medication.

Topics: Adult; Cisapride; Clinical Trials as Topic; Double-Blind Method; Female; Gastric Emptying; Gastrointestinal Motility; Humans; Intestinal Pseudo-Obstruction; Male; Manometry; Middle Aged; Piperidines; Random Allocation

Topics: Cisapride; Clinical Trials as Topic; Double-Blind Method; Humans; Intestinal Pseudo-Obstruction; Piperidines; Postoperative Complications; Random Allocation

Gastrointestinal side effects of chemotherapy are an under-recognized clinical problem, leading to dose reduction, delays and cessation of treatment, presenting a constant challenge for efficient and tolerated anti-cancer treatment. We have found that oxaliplatin treatment results in intestinal dysfunction, oxidative stress and loss of enteric neurons. BGP-15 is a novel cytoprotective compound with potential HSP72 co-inducing and PARP inhibiting properties. In this study, we investigated the potential of BGP-15 to alleviate oxaliplatin-induced enteric neuropathy and intestinal dysfunction.. Balb/c mice received oxaliplatin (3 mg·kg. Oxaliplatin-induced neuronal loss increased the proportion of neuronal NO synthase-immunoreactive neurons and increased levels of mitochondrial superoxide and cytochrome c in the myenteric plexus. These changes were correlated with an increase in PARP-2 immunoreactivity in the colonic mucosa and were attenuated by BGP-15 co-treatment. Significant delays in gastrointestinal transit, intestinal emptying and pellet formation, impaired colonic motor activity, reduced faecal water content and lack of weight gain associated with oxaliplatin treatment were restored to sham levels in mice co-treated with BGP-15.. Our results showed that BGP-15 ameliorated oxidative stress, increased enteric neuronal survival and alleviated oxaliplatin-induced intestinal dysfunction, suggesting that BGP-15 may relieve the gastrointestinal side effects of chemotherapy.

Topics: Animals; Antineoplastic Agents; Colon; Enteric Nervous System; Enzyme Inhibitors; Gastrointestinal Motility; Gastrointestinal Transit; Intestinal Pseudo-Obstruction; Male; Mice; Mice, Inbred BALB C; Neurons; Organ Culture Techniques; Organoplatinum Compounds; Oxaliplatin; Oximes; Piperidines; Treatment Outcome

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: No cost-effectiveness studies exist in patients after radical cystectomy for the routine use of alvimopan for the prevention of postoperative ileus. The present study provides a reasonable estimate of the cost-effectiveness of alvimopan for the prevention of postoperative ileus in the patient after radical cystectomy.. To determine if the cost of administering alvimopan, to help restore bowel function after abdominal surgery, to all patients undergoing radical cystectomy (RC) is cost prohibitive.. A cost-effective analysis was conducted from a healthcare payer perspective using a decision-tree model that incorporated direct healthcare costs and probabilities associated with the possible events and outcomes. Sensitivity analyses were conducted on the influence of the cost and effectiveness of the drug, the probability of POI in RC patients, and the extended length of stay (LOS) as a result of POI. Precision in estimates was determined using probabilistic sensitivity analyses with 5000 Monte-Carlo simulations.. Under the base case assumption, the additional cost of a patient's LOS related to POI was $10 246 per person. Under the assumption that 15.6% of patients will have POI, the mean cost associated with POI in a cohort of patients not treated with alvimopan was $1597 (90% confidence interval [CI] $1335-1875) per patient. Conversely, the routine use of alvimopan for all patients undergoing RC was associated with a mean POI-associated cost of $1495(90% CI $1312-1696) per person, which represents the cost of alvimopan ($700 per hospitalisation) and a 50% reduction in the rate of POI. Sensitivity analyses revealed that there is a cost savings with the routine use of alvimopan under the following conditions: the POI results in extending LOS by ≥3.5 days, POI occurs in ≥14% of patients undergoing RC, or the drug results in a relative risk reduction of ≥44%.. Routine use of perioperative alvimopan may not be cost prohibitive because of its influence on POI rate and associated costs. The cost-effectiveness of alvimopan is influenced by the POI incidence and the degree to which the drug can decrease the LOS.

Topics: Cost-Benefit Analysis; Cystectomy; Female; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Intestinal Pseudo-Obstruction; Length of Stay; Male; Piperidines; Postoperative Period

Topics: Analgesics, Opioid; Anesthetics; Gastrointestinal Agents; Humans; Intestinal Pseudo-Obstruction; Intubation, Gastrointestinal; Naltrexone; Piperidines; Postoperative Complications; Preoperative Care; Quaternary Ammonium Compounds

Topics: Aged; Cholinesterase Inhibitors; Dementia; Donepezil; Humans; Indans; Intestinal Pseudo-Obstruction; Male; Piperidines; Withholding Treatment

The endocannabinoid system (i.e., the cannabinoid receptors and their endogenous ligands) plays an important role in the physiological control of intestinal motility. However, its participation in intestinal pathological states is still poorly understood. In the present study, we investigated the possible role of the endocannabinoid system in the pathogenesis of paralytic ileus, a pathological state consisting of decreased intestinal motility following peritonitis, surgery, or other noxious situations. Ileus was induced by i.p. administration of acetic acid, and gastrointestinal propulsion was assessed by the charcoal method. Endocannabinoid levels were measured by isotope-dilution gas chromatography-mass spectrometry, whereas cannabinoid CB1 receptors were identified by immunohistochemistry. Acetic acid administration inhibited gastrointestinal transit (ileus), and this effect was accompanied by increased levels of the endocannabinoid anandamide compared with control mice and by overexpression of CB1 receptors in myenteric nerves. Furthermore, acetic acid-induced ileus was alleviated by the CB1 receptor antagonist SR141716A and worsened by VDM11, a selective inhibitor of anandamide cellular uptake (and hence inactivation). From these findings, it can be concluded that the intestinal hypomotility typical of paralytic ileus is due, at least in part, to the enhancement of anandamide levels and CB1 expression during this condition, and that selective, nonpsychotropic CB1 receptor antagonists could represent new drugs to treat this disorder.

Topics: Animals; Arachidonic Acids; Cannabinoid Receptor Modulators; Endocannabinoids; Enteric Nervous System; Gastrointestinal Motility; Intestinal Pseudo-Obstruction; Intestine, Small; Mice; Models, Biological; Neurons; Piperidines; Polyunsaturated Alkamides; Pyrazoles; Receptors, Cannabinoid; Receptors, Drug; Rimonabant

Cisapride has been used in the treatment of chronic intestinal pseudo-obstruction with some success; however, the use of cisapride in the treatment of acute pseudo-obstruction has not been adequately studied. We describe a case of acute intestinal pseudo-obstruction successfully treated with cisapride. To our knowledge, this is the second such case reported in the English language literature. Our patient's acute intestinal pseudo-obstruction was probably precipitated by pneumonia and sepsis, and the prompt resolution of his intestinal pseudo-obstruction after initiation of cisapride therapy (despite progressive deterioration of his overall clinical status) implicates cisapride as the cause of the improved intestinal function. Therefore, we suggest that a trial of cisapride be considered for patients with acute intestinal pseudo-obstruction when other therapeutic maneuvers have failed.

Topics: Acute Disease; Cisapride; Colonic Diseases; Fatal Outcome; Humans; Intestinal Pseudo-Obstruction; Male; Middle Aged; Parasympathomimetics; Piperidines; Radiography

In a 75-year-old man acute intestinal pseudo-obstruction was observed during treatment with baclofen 20 mg daily. After discontinuation of the baclofen he recovered completely. No other cause of intestinal obstruction could be demonstrated. Baclofen is an agonist of spinal GABA receptors. It is used in the treatment of spasticity caused by multiple sclerosis or other diseases of the spinal cord, in particular traumatic lesions. Physicians should be aware of this possible adverse effect of baclofen.

Topics: Aged; Anti-Ulcer Agents; Baclofen; Bisacodyl; Cathartics; Cisapride; Humans; Intestinal Pseudo-Obstruction; Male; Muscle Relaxants, Central; Piperidines; Radiography

We report two cases of intestinal pseudoobstruction caused by visceral smooth muscle involvement due to myotonic muscular dystrophy. Two patients with myotonic muscular dystrophy presented with abdominal pain, distention, constipation, and vomiting. The exclusion of mechanical obstruction by plain abdominal radiography, contrast studies, and colonoscopy led to the diagnosis of intestinal pseudoobstruction. Diagnosis was confirmed by manometric and cineradiographic findings of abnormal intestinal motility. Conservative management including laxatives and cisapride led to the resolution of the pseudoobstruction syndrome and long-term remission without relapses during a two year follow-up. In patients with known myotonic dystrophy the occurrence of intestinal pseudoobstruction should be considered in order to avoid unnecessary laparotomies.

Topics: Cathartics; Cisapride; Female; Follow-Up Studies; Humans; Intestinal Pseudo-Obstruction; Male; Manometry; Middle Aged; Muscle, Smooth; Myotonic Dystrophy; Piperidines; Radiography; Sympathomimetics

A case is reported of a 68-year-old woman admitted in the ICU for acute exacerbation of a chronic obstructive respiratory disease. The trachea was intubated and the lungs ventilated mechanically. She received sedation including midazolam and phenoperidine 1 mg.h-1. On the 6th day, she experienced a massive colonic dilation (caecal diameter of 10 cm at X-ray examination). A colonoscopy was performed which showed the absence of obstruction, confirmed the diagnosis of pseudo-obstruction of the colon and allowed a decompression which was inefficient. A new colonoscopic decompression was performed on the 8th day, without prolonged effect. At that time, the patient was given cisapride in her gastric tube (80 mg). This treatment restarted the bowel movements within 48 hours and the caecal diameter decreased immediately to 7 cm. Cisapride was maintained for 10 days and mechanical ventilation for 30 days. No further dilation occurred during this time and the patient was discharged from the ICU. Few cases of Ogilvie's syndrome successfully treated with cisapride have been reported in the literature. The efficacy of this agent for the treatment of Ogilvie's syndrome remains to be assessed in a controlled study.

Topics: Aged; Cisapride; Colonic Diseases; Colonoscopy; Female; Gastrointestinal Motility; Humans; Intestinal Pseudo-Obstruction; Piperidines; Respiration, Artificial

Topics: Child; Chronic Disease; Cisapride; Electromyography; Gastrointestinal Motility; Gastrointestinal Transit; Humans; Intestinal Pseudo-Obstruction; Manometry; Myoelectric Complex, Migrating; Piperidines; Serotonin Antagonists

A 43-year-old man with chronic intestinal pseudo-obstruction is presented. He had undergone two laparotomies in an attempt to eliminate the cause of repeated episodes suggestive of obstruction. Gastrointestinal manometry showed severe abnormalities compatible with the diagnosis of chronic intestinal pseudo-obstruction. Laboratory tests indicated the presence of intestinal malabsorption and villous atrophy. A gluten-free diet accompanied by 10 days of treatment with tetracycline and 2 short periods of treatment with cisapride led to gradual, but apparently complete, resolution of the pseudo-obstructive syndrome. Repeated manometric studies showed progressive normalization of both the fasting and postprandial upper gastrointestinal motor pattern.

Topics: Adult; Chronic Disease; Cisapride; Fasting; Gastrointestinal Motility; Humans; Intestinal Pseudo-Obstruction; Male; Manometry; Piperidines; Tetracycline

Topics: Cisapride; Colonic Diseases; Combined Modality Therapy; Hirschsprung Disease; Humans; Ileostomy; Infant; Intestinal Pseudo-Obstruction; Parenteral Nutrition, Total; Piperidines

Topics: Cisapride; Constipation; Diarrhea; Domperidone; Dumping Syndrome; Gastric Emptying; Gastrointestinal Motility; Humans; Intestinal Diseases; Intestinal Pseudo-Obstruction; Intestine, Small; Metoclopramide; Motilin; Parasympathomimetics; Piperidines; Serotonin Antagonists; Stomach Diseases

A case of chronic intestinal pseudoobstruction secondary to systemic amyloidosis in a patient with multiple myeloma is described. Gastrointestinal symptoms and indices of nutrition improved markedly after commencing treatment with cisapride, which may have been responsible for relatively prolonged survival compared with similar reported cases.

Topics: Amyloidosis; Cisapride; Female; Humans; Intestinal Diseases; Intestinal Pseudo-Obstruction; Middle Aged; Piperidines; Serotonin Antagonists; Stomach Diseases

Topics: Aged; Cisapride; Colonic Pseudo-Obstruction; Female; Humans; Intestinal Pseudo-Obstruction; Male; Piperidines; Serotonin Antagonists

A 73-yr-old white woman admitted with lobar pneumonia and congestive heart failure developed progressive colonic pseudoobstruction (Ogilvie's syndrome) 2 days after admission which was unrelieved by diatrizoate meglumine (Gastrografin, Squibb Canada, Montreal) enema and rectal tube. Cisapride, a new gastrointestinal prokinetic agent, was administered intravenously with full resolution of the syndrome. To the authors' knowledge, this is the first reported case of successful treatment of acute colonic pseudoobstruction with cisapride.

Topics: Acute Disease; Aged; Cisapride; Colonic Diseases; Colonic Pseudo-Obstruction; Drug Evaluation; Drugs, Investigational; Female; Humans; Infusions, Intravenous; Intestinal Pseudo-Obstruction; Piperidines; Serotonin Antagonists; Time Factors

Topics: Cisapride; Dyspepsia; Gastric Emptying; Gastroesophageal Reflux; Humans; Intestinal Pseudo-Obstruction; Piperidines; Serotonin Antagonists

Topics: Adult; Aged; Cisapride; Constipation; Dyspepsia; Female; Humans; Intestinal Pseudo-Obstruction; Male; Middle Aged; Pilot Projects; Piperidines; Prospective Studies; Simethicone

Paralytic ileus and intestinal adhesions are common events following intra-abdominal surgery. The theoretical hypothesis 'that stimulation of the postoperative bowel will reduce intestinal adhesions' was studied in a rat model for intestinal adhesions in which postoperative bowel motility was pharmacologically manipulated. Immediate postoperative stimulation of gastrointestinal motility by the prokinetic agent, Cisapride, resulted in a significant reduction in both the number and extent of adhesions. Inhibition of postoperative intestinal motility with the anticholinergic agent, atropine, resulted in a greater number of more dense adhesions involving an increased length of bowel.

Topics: Animals; Cisapride; Female; Gastrointestinal Motility; Intestinal Diseases; Intestinal Pseudo-Obstruction; Piperidines; Postoperative Complications; Rats; Rats, Inbred Strains; Serotonin Antagonists; Tissue Adhesions

This is a case report of a previously asymptomatic 11-year-old boy who developed chronic intestinal pseudo-obstruction. Barium studies revealed grossly disordered motility of the proximal small bowel, and ganglion cells in a gastric biopsy were mildly abnormal. Treatment with conventional prokinetic agents and gastrojejunostomy were ineffective. Intravenous cisapride induced an immediate remission, which has been maintained subsequently by rectal administration of the drug.

Topics: Administration, Rectal; Child; Chronic Disease; Cisapride; Humans; Injections, Intravenous; Intestinal Pseudo-Obstruction; Intestine, Small; Male; Piperidines

Chronic intestinal pseudo-obstruction describes a heterogeneous group of disorders characterized by signs and symptoms of intestinal obstruction in the absence of a mechanical lesion. We studied antroduodenal motility in 13 children with pseudo-obstruction. The diagnosis was based on radiographic evidence in all, surgery in 11, and specific pathologic features in four. Antroduodenal motility was abnormal in all 13. Qualitative abnormalities in the patterns of antroduodenal contractions permitted separation into groups: (1) postprandial hypomotility (n = 3), (2) absent migrating motor complexes, with phase 3-like activity at the start of meals (neuropathic variety) (n = 5) (3) very low amplitude or absent contractions (myopathic variety) (n = 2); the remaining patients (n = 3) had other distinctive abnormalities. Cisapride, a new gastrointestinal prokinetic drug, stimulated proximal duodenal contractions in the 30 minutes after a meal in nine of 10 patients tested. These studies indicate that antroduodenal manometry is useful for characterizing intestinal pseudo-obstruction, and cisapride stimulates postprandial duodenal contractions in patients with pseudo-obstruction.

Topics: Child; Child, Preschool; Cisapride; Duodenum; Female; Gastrointestinal Motility; Humans; Infant; Intestinal Pseudo-Obstruction; Male; Piperidines; Pyloric Antrum

Chronic intestinal pseudoobstruction is a clinical syndrome whose pathophysiology, objective diagnosis, and treatment are poorly understood. We investigated 8 patients with this syndrome in whom intestinal dysmotility was established manometrically by two or more of the following criteria: abnormal configuration or propagation of interdigestive motor complexes, sustained incoordinate pressure activity, non-propagated bursts of phasic pressure activity, and failure of a solid-liquid meal to induce a fed pattern. To establish the functional impairment and region of the gut primarily affected by the disease, we quantified radio-scintigraphically the gastrointestinal transit of the solid (131I-fiber) and liquid (99 mTc-DTPA) components of a meal. Our techniques allowed us to quantify separately gastric emptying and pylorus-to-cecum transit. Furthermore, we evaluated the effects of a new prokinetic agent, cisapride. Gastric emptying times in pseudoobstruction were not significantly delayed; however, transit times through the small bowel (t1/2) were markedly prolonged [solids, 235 +/- 43 min (mean +/- SEM) vs. 138 +/- 25 controls, p less than 0.05; liquids, 310 +/- 67 vs. 181 +/- 28 controls, p = 0.07]. Cisapride was effective in reducing the delayed intestinal transit time to within the normal range (delta solids = -115 +/- 25 min; delta liquids = -146 +/- 71 min; p less than 0.05 for both). These studies suggest that intestinal dysmotility in this group of patients with pseudoobstruction was associated with delayed small bowel transit of radiolabeled solid and liquid components of chyme. Cisapride can restore to normal the delayed transit, indicating that it may potentially correct the impaired propulsive activity in the small bowel of these patients.

Topics: Adult; Cisapride; Eating; Female; Gastric Emptying; Gastrointestinal Motility; Humans; Intestinal Obstruction; Intestinal Pseudo-Obstruction; Iodine Radioisotopes; Male; Middle Aged; Pentetic Acid; Piperidines; Technetium; Technetium Tc 99m Pentetate

Topics: Aged; Antidiarrheals; Humans; Intestinal Obstruction; Intestinal Pseudo-Obstruction; Loperamide; Male; Middle Aged; Piperidines

Topics: Antidiarrheals; Humans; Intestinal Obstruction; Intestinal Pseudo-Obstruction; Loperamide; Male; Piperidines

Topics: Child, Preschool; Humans; Infant; Intestinal Obstruction; Intestinal Pseudo-Obstruction; Loperamide; Piperidines

Topics: Diarrhea, Infantile; Humans; Infant; Intestinal Obstruction; Intestinal Pseudo-Obstruction; Loperamide; Piperidines

Topics: Acetazolamide; Chlorothiazide; Intestinal Obstruction; Intestinal Pseudo-Obstruction; Piperidines