piperidines and Ileus

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

Post-operative ileus (POI) and delayed return of gastrointestinal (GI) function are common complications after colorectal surgery. There is a lack of uniformity in enhanced recovery protocols (ERPs) with regards to interventions used to target these complications. This systematic review aims to categorize and summarize management recommendations available from published ERPs.. A systematic search of Ovid MEDLINE, Embase, Cochrane Library and PubMed databases was performed from January 1990 to May 2018. All studies publishing enhanced recovery or fast-track or multimodal pathway protocols for colorectal surgery in their full-text were included. Data on interventions aimed at reducing the duration of POI were extracted, as well as references quoted to support specific interventions.. Of 481 manuscripts screened, 37 published ERPs were identified from 37 studies (18 cohort, seven historical-control, five guidelines, four randomized controlled trials, one randomized controlled trial protocol, one case series and one narrative review). The most commonly recommended interventions were magnesium-based laxatives (18 of 37, 48.6%), chewing gum (13 of 37, 35.1%), Alvimopan (6 of 37, 16.2%), lactulose (4 of 37, 10.8%), neostigmine (2 of 37, 5.4%) and bisacodyl (2 of 37, 5.4%). Geographical trends were noted for the various interventions, but high-quality evidence was only referenced to support the use of Alvimopan.. ERP recommendations specific to interventions targeting POI and return of GI function are varied. While laxatives are the most commonly recommended intervention, there is only weak evidence reported to support this practice.

Topics: Bisacodyl; Chewing Gum; Colonic Diseases; Humans; Ileus; Lactulose; Neostigmine; Piperidines; Postoperative Complications; Recovery of Function; Rectal Diseases

Alvimopan is used in abdominal surgery to reduce postoperative ileus in patients undergoing small bowel resections with primary anastomosis. The role and efficacy of alvimopan in patients undergoing radical cystectomy with urinary diversion is not well understood.. To assess the effects of alvimopan in the context of enhanced recovery pathways compared to enhanced recovery pathways alone for perioperative bowel dysfunction in patients undergoing radical cystectomy.. The terms alvimopan and cystectomy were used to search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. We also reviewed abstracts from the past four years (2013 to 2016) of the American Urologic Association, Society of Urologic Oncology, and American Society of Clinical Oncology Genitourinary Cancers.. We searched for randomized controlled trials that compared alvimopan to placebo.. This study was based on a published protocol. We performed a comprehensive search of multiple databases including CENTRAL in the Cochrane Library, MEDLINE, Embase, LILACS, Web of Science, Scopus and Biosis, which we last updated on 6 February 2017. We also searched abstract proceedings for major relevant meetings (2013 to 2016), databases of the grey literature, trial registries, citations of relevant reviews and contacted clinical experts and the drug manufacturer.Two independent reviewers screened the literature in two stages (title and abstract, full-text) using Covidence software. Two independent reviewers assessed the risk of bias on a 'per outcome' basis using the Cochrane 'Risk of bias; tool and rated the quality of evidence according to GRADE. Results of the single eligible trial were reported in a 'Summary of findings' table based on an intention-to-treat analysis.. Based on a single trial and moderate-quality evidence, alvimopan reduced the time to reach a composite endpoint of tolerance of solid food and documented bowel movements (hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.41 to 2.23). This represents 165 more patients (109 more to 207 more) per 1000 meeting this endpoint within 10 days of surgery. Based on moderate-quality evidence, alvimopan reduced the time to hospital discharge (HR 1.67, 95% CI 1.38 to 2.01). This represents 138 more patients (82 more to 198 more) per 1000 being discharged within 10 days of surgery. Also based on moderate-quality evidence, alvimopan was associated with a reduced risk of major adverse events (risk ratio (RR) 0.28, 95% CI 0.18 to 0.44) representing 355 fewer patients (404 fewer to 276 fewer) with major adverse events per 1000. We downgraded this outcome for indirectness as it included adverse events that we did not consider major.In terms of secondary outcomes, alvimopan did not appear to alter the rate of readmission (RR 0.89, 95% CI 0.59 to 1.33), change the rate of any cardiovascular event (RR 0.54, 95% CI 0.27 to 1.05) or alter the mean narcotic pain medication use (mean difference 0, 95% CI 14.08 fewer to 14.08 more morphine equivalents). The quality of evidence was moderate for all three outcomes. Based on high-quality evidence, alvimopan reduced the rate of nasogastric tube replacement (RR 0.31, 95% CI 0.16 to 0.59). We did not find evidence for the drug's impact on rates of parenteral nutrition. All outcomes were short term and limited to a 30-day time horizon.Based on the existence of only one trial, we were unable to perform any subgroup or sensitivity analyses.. In patients undergoing radical cystectomy and urinary diversion, the use of alvimopan administered as part of an enhanced recovery pathway for a limited duration (up to 15 doses for up to seven days) probably reduces the time to tolerance of solid food, time to hospital discharge and rates of major adverse events. Readmission rates, rates of cardiovascular events and narcotic pain requirements are probably similar. The need for reinsertion of nasogastric tubes is reduced. We found no evidence for the impact on rates of parenteral nutrition within 30 postoperative days.

Topics: Cardiovascular Diseases; Cystectomy; Defecation; Eating; Gastrointestinal Agents; Humans; Ileus; Patient Discharge; Patient Readmission; Piperidines; Postoperative Complications; Randomized Controlled Trials as Topic; Recovery of Function; Time Factors; Urinary Diversion

Prolonged ileus is a common complication following gastrointestinal surgery, with an incidence of up to 40 %. Investigations examining pharmacological treatment of ileus have proved largely disappointing; however, recently, several compounds have been shown to have benefited when used as prophylaxis to prevent ileus.. This review aimed to evaluate the safety and efficacy of compounds which have been recently developed or repurposed to reduce bowel recovery time, thereby preventing ileus.. Data were taken from a systematic review of the MEDLINE, EMBASE and Cochrane Library Databases, in addition to manual searching of reference lists up to April 2015. No limits were applied.. Only randomized trials were eligible for inclusion.. Opioid receptor antagonists, ghrelin receptor agonists and serotonin receptor agonists used for the prevention of postoperative ileus in gastrointestinal surgery.. Outcomes of time to first defecation, first flatus and composite bowel recovery endpoints (GI2 and GI3) were used to determine efficacy. Pooled treatment effects were presented as the standard mean difference or as hazard ratios alongside the corresponding 95 % confidence intervals. Risk of bias was assessed using the Cochrane risk of bias framework.. A total of 17 studies were included in the final analysis. The μ-opioid receptor antagonist alvimopan and serotonin receptor agonists appeared to significantly shorten the duration of ileus. The use of Ghrelin receptor agonists did not appear to have any effect in five trials. No publication bias was detected.. Most of the trials were poorly reported and of mixed quality. Future studies must focus on the development of a set of core outcomes.. There is evidence to make a strong recommendation for the use of alvimopan in major gastrointestinal surgery to reduce postoperative ileus. Further randomized trials are required to establish whether serotonin receptor agonists are of use. Identifying a low-cost compound to promote bowel recovery following surgery could reduce complications and shorten duration of hospital admissions.

Topics: Abdomen; Digestive System Surgical Procedures; Gastrointestinal Agents; Humans; Ileus; Narcotic Antagonists; Piperidines; Postoperative Complications; Receptors, Ghrelin; Serotonin Receptor Agonists; Treatment Outcome

To assess the efficacy and safety of alvimopan in conjunction with enhanced recovery strategy, compared with this strategy alone, in management of postoperative ileus in patients undergoing open abdominal surgery.. Electronic databases were comprehensively searched for relevant randomized controlled trials. We were interested in doses of 6 and 12 mg. The efficacy end points included the time to recovery of full gastrointestinal (GI) function (a composite end point measured by the time to first toleration of solid food [SF] and the time to first passage of stool, GI-2), the recovery of upper (SF) or the lower (the time to first bowel movement, BM) GI function, and the length of hospital stay (the time to discharge order written). Safety end points included GI-related, non-GI-related, and serious adverse events. These parameters were all analyzed by RevMan 5.3 software.. Nine randomized controlled trials involving 4075 patients were enrolled in this study. The pooled results showed that alvimopan significantly decreased the time to GI-2 recovery (6 mg, hazard ratio [HR] = 1.45, P < 0.00001; 12 mg, HR = 1.59, P < 0.00001), BM (6 mg, HR = 1.54, P < 0.00001; 12 mg, HR = 1.74, P = 0.0002), and the time to discharge order written (6 mg, HR = 1.37, P < 0.00001; 12 mg, HR = 1.34, P < 0.00001) compared with the placebo group. However, SF was significantly reduced in 6 mg group (HR = 1.23, P = 0.008) rather than 12 mg group (HR = 1.14, 95% confidence interval 1.00, 1.30, P = 0.04). The incidence of some GI-related and serious adverse events were significantly lower in the alvimopan group than the placebo group, and the dose of 12 mg was superior to 6 mg in this regard.. Alvimopan can accelerate recovery of GI function (especially for the lower GI tract), shorten the length of hospital stay, and reduce postoperative ileus-related morbidity without compromising opioid analgesia in an enhanced recovery setting.

Topics: Abdomen; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Gastrointestinal Agents; Humans; Ileus; Length of Stay; Models, Statistical; Piperidines; Postoperative Care; Postoperative Complications; Treatment Outcome

Bladder cancer is the most expensive cancer to treat from diagnosis to death. Frequent disease recurrence, intense follow-up, and expensive, invasive techniques for diagnosis and treatment drive these costs for non-muscle invasive bladder cancer. Fluorescence cystoscopy increases the detection of superficial bladder cancer and reduces costs by improving the quality of resection and reducing recurrences. Radical cystectomy with intestinal diversion is the mainstay of treatment of invasive disease; however it is associated with substantial cost and morbidity. Increased efforts to improve the surgical management of bladder cancer while reducing the cost of treatment are increasingly necessary.

Topics: Cost-Benefit Analysis; Cystectomy; Cystoscopy; Gastrointestinal Agents; Health Care Costs; Humans; Ileus; Length of Stay; Piperidines; Robotic Surgical Procedures; Urinary Bladder Neoplasms

Prolonged postoperative ileus (POI) is the predominant cause of extended hospitalization after bowel resection surgery. Alvimopan accelerates gastrointestinal recovery, potentially reducing health care costs. We examined the value of alvimopan in reducing prolonged POI and length of stay for patients undergoing abdominal surgery using different definitions of POI.. We developed a decision analytic model to examine costs and outcomes associated with postoperative treatment with either an accelerated care pathway (ACP) only or alvimopan+ACP. To represent an overall perspective for alvimopan, data from four phase 3 bowel resection trials and one phase 4 radical cystectomy trial were used to populate the model with 3 different definitions of POI. The period analyzed included start of surgery to 7 days post discharge. Costs were obtained from standard US costing sources and are reported in 2015 US dollars. Due to variations in published definitions of POI, alternative definitions based on adverse event reports, NG tube insertion, and time to food toleration were examined.. The combined clinical trial data included 1,003 ACP and 1,013 alvimopan+ACP patients. When POI was reported as an adverse event, the incidence of POI was significantly lower with alvimopan+ACP (n = 70 [7%]) vs ACP alone (n = 148 [15%]; p < 0.0001). Time to discharge order written was shorter for patients with POI who were treated with alvimopan+ACP than with ACP (202 ± 115 hours vs 266 ± 138 hours; p < 0.0001). As a result, costs were $731 lower with alvimopan+ACP ($17,835) vs ACP ($18,566). Alternative definitions of POI produced similar results.. The addition of alvimopan to existing treatment pathways for patients undergoing abdominal surgery can reduce overall hospital costs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Cystectomy; Decision Trees; Digestive System Surgical Procedures; Female; Gastrointestinal Agents; Hospital Costs; Humans; Ileus; Length of Stay; Male; Middle Aged; Models, Statistical; Piperidines; Postoperative Care; Postoperative Complications; United States; Young Adult

Transient ileus is a normal physiologic process after surgery. When prolonged, it is an important contributor to postoperative complications, increased length of stay and increased healthcare costs. Efforts have been made to prevent and manage postoperative ileus; alvimopan is an oral, peripheral μ-opioid receptor antagonist, and the only currently US FDA-approved medication to accelerate the return of gastrointestinal function postoperatively.

Topics: Administration, Oral; Digestive System Surgical Procedures; Gastrointestinal Agents; Humans; Ileus; Intestine, Large; Intestine, Small; Narcotic Antagonists; Piperidines; Receptors, Opioid, mu; Recovery of Function; Risk Factors; Treatment Outcome

For radical cystectomy, historical practice trends have favored the use of preoperative bowel preparations to reduce complications, including surgical site infections, ileus, and anastomotic leaks. However, emerging data has questioned this practice. Postoperative cystectomy care also remains in flux, as new pharmacologic agents that may potentiate earlier return of bowel function are studied. We review the current literature with regards to preoperative and postoperative cystectomy bowel management.

Topics: Anti-Bacterial Agents; Cathartics; Chemoprevention; Cystectomy; Gastrointestinal Agents; Humans; Ileus; Piperidines; Postoperative Care; Postoperative Complications; Preoperative Care; Surgical Wound Infection; Urinary Diversion

Peripherally acting mu-opioid receptor antagonists methylnaltrexone and alvimopan are a new class of drugs designed to reverse opioid-induced side-effects on the gastrointestinal system without compromising pain relief. This article gives an overview of the pharmacology, the efficacy, and adverse effects of these drugs. Both compounds seem to be generally well tolerated and effective for the treatment of opioid-related bowel dysfunction and postoperative ileus. Methylnaltrexone recently received approval by the US Food and Drug Administration (FDA) and the European Medicines Agency for treatment of opioid-related bowel dysfunction in patients with advanced illness. Alvimopan was recently approved by the FDA for treatment of postoperative ileus, but the use of the drug is restricted to inpatients because it has been associated with an increased rate of myocardial infarction. Further research should assess the effectiveness and safety of these drugs in clinical practice.

Topics: Analgesics, Opioid; Blood-Brain Barrier; Drug Approval; Europe; Humans; Ileus; Myocardial Infarction; Naltrexone; Narcotic Antagonists; Patient Selection; Piperidines; Postoperative Complications; Quaternary Ammonium Compounds; Research Design; Safety; United States; United States Food and Drug Administration

The duration of postoperative ileus following abdominal surgery is quite variable, and prolonged postoperative ileus is an iatrogenic phenomenon with important influence on patient morbidity, hospital costs and length of stay in hospital. Adequate treatment for prolonged postoperative ileus is important to improve patient morbidity and clinical efficiency. Both clinical and pharmacological management strategies have improved rapidly over the last decade, and appropriate and timely management using multimodal techniques should be used for optimal care. In this review, we define postoperative ileus, describe the pathogenesis and briefly discuss clinical management before detailing potential pharmacologic management options.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Anti-Inflammatory Agents, Non-Steroidal; Bisacodyl; Cathartics; Cisapride; Dihydroergotamine; Humans; Ileus; Inflammation; Naltrexone; Neostigmine; Parasympathomimetics; Piperidines; Postoperative Complications; Propranolol; Quaternary Ammonium Compounds; Receptors, Opioid, mu; Serotonin Receptor Agonists

The efficacy, safety, pharmacology, pharmacokinetics, drug-drug interactions, and administration of alvimopan for postoperative ileus are reviewed.. Alvimopan is a selective mu-opioid receptor antagonist with no central nervous system activity. When orally administered after partial small- or large-bowel resection in patients with primary anastomosis, alvimopan shortened the return of bowel function and time to discharge by approximately one day without compromising analgesia. Alvimopan was not shown to be beneficial on these same outcomes after hysterectomy and has not been studied in other surgical populations. Alvimopan is generally well tolerated, with the frequency of adverse events being similar to placebo when used postoperatively for one week or less. Long-term studies of alvimopan in opioid-induced bowel dysfunction have shown an association with adverse cardiovascular outcomes, neoplasms, and fractures. Because of these concerns, the Entereg Access Support and Education program was developed. The recommended dosage of alvimopan is 12 mg administered with a sip of water 30 minutes to five hours before surgery, followed by 12 mg twice daily beginning the day after surgery for a maximum of seven days, 15 total doses, or until discharge. There is a limited amount of pharmacoeconomic analysis concerning alvimopan.. Alvimopan, a peripherally acting mu-opioid receptor antagonist, is a novel agent for the treatment of postoperative ileus. It appears to decrease the duration of postoperative ileus and hospitalization by approximately one day, theoretically offsetting its acquisition costs. Unresolved long-term safety issues, a limited indication, and its restricted-access program are likely to hinder its widespread use in the surgical population.

Topics: Animals; Humans; Ileus; Piperidines; Postoperative Complications; Receptors, Opioid, mu

To summarize the evidence on pharmacologic options in preventing postoperative ileus (POI).. The Cochrane Database of Reviews and OVID databases and Food and Drug Administration (FDA) Web site were searched (1950-April 2009) using the term postoperative ileus.. Meta-analyses and randomized controlled trials were included for review. The FDA Web site was searched for clinical reviews and label information for drugs indicated for the prevention of POI.. Three meta-analyses, 2 on gum-chewing and 1 on alvimopan, and 18 clinical trials were identified. Only gum chewing and alvimopan were effective in preventing POI. Gum chewing reduced the time to first flatus and bowel movement (weighted mean difference 21h; p = 0.0006 and 33h; p = 0.0002, respectively). In one meta-analysis, gum chewing significantly reduced length of stay (LOS) by 2.4 days (p < 0.00001) but this was not replicated in the second meta-analysis. Alvimopan shortened the time to reach a composite endpoint of solid food intake, plus/minus flatus, and bowel movement (93 vs 105 h; p < 0.001). A higher incidence of myocardial infarction was observed in a 12-month study of alvimopan for the treatment of opioid-induced bowel dysfunction, but not in studies in patients undergoing bowel resection. Alvimopan decreased the time to written hospital discharge order (hazard ratio 1.35; p < 0.01), while the significance of a reduction in LOS (0.2-1.3 days) was not reported.. Gum chewing and alvimopan are effective in preventing POI, but given safety concerns and higher cost with alvimopan, gum chewing may be preferred.

Topics: Chewing Gum; Clinical Trials as Topic; Drug Costs; Gastrointestinal Agents; Humans; Ileus; Piperidines; Postoperative Care; Postoperative Complications

Topics: Animals; Humans; Ileus; Piperidines; Postoperative Complications; Randomized Controlled Trials as Topic

Alvimopan is a selective, competitive mu-opioid receptor antagonist with limited oral bioavailability which may be used to reduce length of post-operative ileus.. The study compared alvimopan with placebo following bowel resection or total abdominal hysterectomy.. A meta-analysis of randomized-controlled trials published between 2001 and 2006 of alvimopan vs. placebo was performed. The primary efficacy end-points were composite measures of passage of flatus, stool, and tolerance of solid food (GI-3) and passage of stool and tolerance of solid food (GI-2). The incidence of treatment emergent adverse events was assessed.. Five trials matched the selection criteria, reporting on 2195 patients. A total of 1521 (69.3%) had alvimopan and 674 (30.7%) placebo. GI-3 significantly improved (hazard ratio 1.30; 95% confidence intervals 1.16, 1.45, P < 0.001), as did GI-2 (hazard ratio 1.61; 95% confidence intervals 1.26, 2.05, P < 0.001) on alvimopan 12 mg. Time to discharge (hazard ratio 1.26; 95% confidence intervals 1.13, 1.40, P < 0.001), time to bowel motion (hazard ratio 1.74; 95% confidence intervals 1.29, 2.35, P < 0.001), and time to solid food (hazard ratio 1.14; 95% confidence intervals 1.01, 1.30, P < 0.04) also improved significantly. No difference was noted in the incidence of treatment emergent adverse events.. Alvimopan showed significant advantages over placebo in restoring gastro-intestinal function, and reduced time to discharge following major abdominal surgery, with acceptable side effects.

Topics: Adolescent; Adult; Digestive System Surgical Procedures; Female; Gastrointestinal Motility; Humans; Hysterectomy; Ileus; Middle Aged; Piperidines; Postoperative Complications; Randomized Controlled Trials as Topic; Receptors, Opioid, mu; Recovery of Function; Treatment Outcome

To obtain further analysis regarding specific outcomes and alvimopan doses in bowel resection (BR) patients.. Although postoperative ileus (POI) is common after BR, there is currently no recognized treatment or prevention available. Alvimopan, a novel, peripherally active mu-opioid receptor antagonist, accelerated GI recovery after BR or hysterectomy in 3 phase III trials.. A pooled retrospective subset analysis of BR patients in alvimopan phase III trials was performed. Randomized BR patients received alvimopan 6 mg (n = 397), 12 mg (n = 413), or placebo (n = 402) >or=2 hours before surgery and twice daily until hospital discharge for

Topics: Clinical Trials, Phase III as Topic; Digestive System Surgical Procedures; Gastrointestinal Agents; Humans; Ileus; Intestine, Large; Intestine, Small; Piperidines; Postoperative Complications; Proportional Hazards Models; Randomized Controlled Trials as Topic; Receptors, Opioid, mu

Postoperative ileus (POI), a transient cessation of coordinated bowel motility, occurs to some extent after all major abdominal operations. This analysis examines gastrointestinal (GI) recovery and hospital discharge history in patients undergoing partial bowel resection (BR) or total abdominal hysterectomy (TAH) by laparotomy in the placebo arms of recent phase III alvimopan trials.. This was a pooled post hoc analysis of placebo groups from randomized, double-blind, parallel-group, multicenter trials. All patients were uniformly managed with a standardized accelerated postoperative care pathway to facilitate GI recovery.. Of the 727 BR patients and 140 TAH patients included in this analysis, POI as an adverse event was reported in approximately 14.7% of BR patients and 2.9% of TAH patients, and postoperative nasogastric tube insertion was required in 11.5% of BR patients and 0.8% of TAH patients. Time to first toleration of solid food was almost 2 days longer for BR patients than for TAH patients (BR, 4.1 days; TAH, 2.5 days). Approximately 34.4% of BR patients and 4.2% of TAH patients had discharge orders written 7 days or more after operation. Nearly half (40%) of patients undergoing TAH were discharged from the hospital before GI recovery was complete. Mean postoperative lengths of hospital stay after BR and TAH were 6.6 days and 3.4 days, respectively.. Despite the relatively fast recovery observed with standardized accelerated postoperative care pathway use, POI as an adverse event was still reported in approximately 15% of BR patients and 3% of TAH patients. This analysis provides important clinical insight into the differences in GI recovery patterns and the incidence and impact of POI after BR and TAH.

Topics: Adult; Aged; Clinical Trials, Phase III as Topic; Female; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Hysterectomy; Ileus; Intestines; Male; Middle Aged; North America; Piperidines; Recovery of Function

Methylnaltrexone and alvimopan are two new and potentially useful agents in the management of opioid-induced bowel dysfunction and prevention of postoperative ileus. Both agents have promising prokinetic properties and appear to be capable of reversing the effects of opioids on delayed gastrointestinal transit. This article reviews currently available published literature to provide an overview of the clinical trials and to provide insight for the potential use of these agents for patients requiring opioid based analgesia. These compounds represent a new class of compounds that may impact the therapeutics for opioid induced bowel dysfunction as well as postoperative ileus.

Topics: Analgesics, Opioid; Gastrointestinal Transit; Humans; Ileus; Intestinal Diseases; Naltrexone; Narcotic Antagonists; Piperidines; Postoperative Complications; Quaternary Ammonium Compounds

The adverse effects of opioids are well documented. Because opioid receptors have a wide-ranging anatomic distribution, the effects subsequent to opioid binding, both good and bad, occur centrally and in the periphery. Postoperative strategies to reduce opioid burden, therefore, are in the patient's best interest. Multimodal analgesia is the key towards balancing the need for opioids while simultaneously reducing their burden. Alternative anesthesia and analgesia options such as regional anesthesia, nonsteroidal anti-inflammatory drugs, or cyclooxygenase-2 enzyme inhibitors should be considered part of multimodal protocols. Familiarity of where these drugs are active in the body and how they can be employed is imperative for all surgical team members. Optimal implementation of multimodal approaches can reduce hospital stay and improve clinical outcomes, including patient satisfaction. Finally, strategies that may help reduce rates of hospital readmission also contribute to overall improved outcome. New peripherally acting mu-opioid-receptor antagonists represent significant progress in the ability of perianesthesia nurses to play an even greater role in achieving these goals. In contrast to older opioid-receptor antagonists, these agents specifically target an important aspect of the multifactorial etiology of postoperative ileus (POI), mu-opioid-receptor-mediated activity in the GI tract. In addition, they do not pass the blood-brain barrier or diminish opioid-mediated analgesia. Advanced clinical trials have already demonstrated the ability of one of these agents, alvimopan, to reduce POI and improve other postoperative outcomes while maintaining adequate analgesia. Combined with other options aimed at reducing opioid burden, alvimopan and similar drugs in development hold promise as part of multimodal protocols to optimize pain management while minimizing postoperative morbidities.

Topics: Analgesia; Analgesics, Opioid; Anesthesia; Anesthesiology; Anti-Inflammatory Agents, Non-Steroidal; Attitude of Health Personnel; Blood-Brain Barrier; Clinical Trials, Phase III as Topic; Humans; Ileus; Length of Stay; Naltrexone; Narcotic Antagonists; Nurse's Role; Outcome Assessment, Health Care; Pain, Postoperative; Patient Satisfaction; Piperidines; Postanesthesia Nursing; Postoperative Care; Postoperative Complications; Quaternary Ammonium Compounds; Receptors, Opioid, mu; Risk Factors

Postoperative ileus (POI) is defined as the impairment of bowel motility that occurs almost universally after major open abdominal procedures, as well as other abdominal and nonabdominal procedures. For the majority of affected patients, POI generally lasts approximately three to five days, but longer duration is not uncommon. The causes of POI are multifactorial, but can be broadly categorized into two groups: those related to the surgical procedure and those related to pharmacologic interventions (opioids). The fact that POI is generally transient and therefore self-limited should not deter the surgical team from seeking improved ways to mitigate its associated adverse effects, which can be substantial and immensely uncomfortable for the patient, and can have far-reaching implications regarding overall hospitalization costs for many types of surgeries. Optimization of POI management and prevention efforts is a responsibility of all members of the surgical team and can drastically affect the overall clinical outcome of major abdominal surgery. Depending on the individual team member's role, different perspectives and strategies may be used to achieve improved outcomes, including but not limited to hospitalization costs related to care and length of stay, resource utilization, and, perhaps most critically, patient quality of life not only immediately after surgery but also after discharge. The ability to reliably and significantly decrease the duration of POI should be readily recognized as an important objective in the management of this condition. Opioids will continue to be a mainstay of postoperative care regimens, but new agents such as peripherally acting mu-opioid-receptor antagonists may offer a unique clinical advantage by helping to reduce the adverse gastrointestinal effects of opioids while preserving their desired benefits for postoperative analgesia.

Topics: Analgesics, Opioid; Causality; Cost of Illness; Hospital Costs; Humans; Ileus; Incidence; Laparotomy; Length of Stay; Naltrexone; Narcotic Antagonists; Nurse's Role; Outcome Assessment, Health Care; Pain, Postoperative; Patient Care Team; Patient Satisfaction; Piperidines; Postanesthesia Nursing; Postoperative Care; Postoperative Complications; Professional Role; Quaternary Ammonium Compounds; Time Factors; Total Quality Management

Postoperative ileus (POI) is frequently experienced by many patients undergoing abdominal operations and other surgical procedures. Postoperative ileus causes physical discomfort and may increase risk for prolonged hospital length of stay. Despite its prevalence, there is currently no accepted standard definition of POI and, consequently, no standardized mode of prevention or treatment; it is no wonder that a variety of management approaches for POI have been developed. Some of these include alternative surgical techniques such as laparoscopic or endoscopic procedures to minimize trauma and help lessen the release of endogenous mediators of POI. Others have evaluated alternate analgesic regimens such as thoracic epidural anesthetics to avoid stimulating opioid receptors in the gut. These approaches have had varying results. Other pharmacologic attempts to reduce POI have focused on the blockade of opioid receptors to prevent opioid-induced GI-related adverse effects. A new class of agents, peripherally acting mu-opioid-receptor antagonists such as methylnaltrexone and alvimopan, may improve the pharmacologic management of POI and reshape the current paradigm of multimodal management of POI. Protocols that incorporate these agents may offer yet another avenue to mitigate the adverse effects of POI, and thus help improve surgical outcomes. To date, alvimopan has been shown in phase 3 clinical trials to significantly reduce the duration of POI while maintaining satisfactory analgesia and reducing length of hospital stay. Combinations of strategies with demonstrated effectiveness such as early feeding, epidural analgesia, laparoscopic surgery, and peripherally acting mu-opioid-receptor antagonists may help transform the management of POI into an effective multimodal paradigm that targets the diverse etiologic factors leading to this common clinical problem. Clearly, all surgical team members are crucial in the optimal implementation of such multimodal approaches.

Topics: Analgesia, Epidural; Analgesics, Opioid; Attitude of Health Personnel; Choice Behavior; Enteral Nutrition; Evidence-Based Medicine; General Surgery; Humans; Ileus; Intubation, Gastrointestinal; Laparoscopy; Laparotomy; Length of Stay; Naltrexone; Narcotic Antagonists; Outcome Assessment, Health Care; Patient Care Team; Patient Selection; Piperidines; Postoperative Care; Postoperative Complications; Practice Guidelines as Topic; Quaternary Ammonium Compounds; Risk Factors

Alvimopan is a novel, peripherally acting mu-opioid antagonist that is being developed for the management of acute postoperative ileus and for the reversal of the delayed gastrointestinal and colonic transit that result in symptoms such as constipation, nausea and motility disorders in patients treated with opiate analgesics. There is a clinical need for effective medications for the treatment of postoperative ileus and opiate-induced constipation and other motility disorders. This review addresses the basic and applied pharmacology and current evidence for the use of the medication, alvimopan, in clinical gastroenterology.

Topics: Animals; Constipation; Gastrointestinal Motility; Humans; Ileus; Narcotic Antagonists; Piperidines; Postoperative Complications; Receptors, Opioid, mu

Alvimopan is a synthetic peripherally restricted mu-receptor opioid antagonist. Alvimopan has a greater affinity for the mu-receptor than the kappa- or sigma-opioid receptors (Ki = 0.77 nM). The polarity of the molecule limits gastrointestinal absorption and central nervous system penetration. It has limited systemic bioavailability and higher affinity for the mu-opioid receptor than naloxone (Ki = 3.7 nM). Completed Phase III trials suggest efficacy in accelerating the recovery of gastrointestinal function after abdominal surgery. Adverse events with all doses have been similar to placebo groups. Further efficacy in alleviating opioid-induced bowel dysfunction in patients with chronic opioid usage has also been demonstrated. This evidence-based review assesses this new drug and discusses its potential role in clinical practice.

Topics: Abdomen; Administration, Oral; Adult; Analgesics, Opioid; Constipation; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Ileus; Male; Middle Aged; Narcotic Antagonists; Piperidines; Postoperative Complications; Randomized Controlled Trials as Topic; Receptors, Opioid, mu

To review the pharmacology, pharmacokinetics, clinical efficacy, safety, dosage, and administration of alvimopan, a peripherally acting mu-opioid receptor antagonist, in the management of postoperative ileus (POI).. A literature search (1980-October 2004) applying the terms alvimopan, ADL 8-2698, and LY246736 was conducted using MEDLINE. Information was also obtained from scientific congress abstracts and data on file with the manufacturer.. Studies and abstracts investigating alvimopan and POI were considered for inclusion; however, they were restricted to English-language articles.. Alvimopan is a novel, peripherally acting mu-opioid receptor antagonist that is currently under evaluation for the management of POI. POI presents significant clinical challenges that can delay patient recovery and contribute to increased morbidity and prolonged hospitalization after surgery. Clinical trials have demonstrated that alvimopan, at oral doses of 6 and 12 mg, can accelerate time to recovery of gastrointestinal (GI) function and time to hospital discharge following abdominal surgery. The incidence of adverse events with alvimopan therapy was shown to be similar to that of placebo.. Alvimopan is well tolerated and effective at accelerating GI recovery and time to discharge in patients who have undergone bowel resection or hysterectomy when administered prior to surgery and twice daily thereafter until discharge or for up to 7 days. Alvimopan potentially offers significant benefits for patients with POI over currently available treatments.

Topics: Clinical Trials as Topic; Costs and Cost Analysis; Drug Interactions; Humans; Ileus; Piperidines; Postoperative Complications

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.

Topics: Adult; Aged; Aged, 80 and over; Defecation; Double-Blind Method; Female; Gastrointestinal Agents; Humans; Hysterectomy; Ileus; Intestine, Large; Intestine, Small; Laparotomy; Male; Middle Aged; Patient Discharge; Piperidines; Placebos; Postoperative Complications; Premedication; Receptors, Opioid, mu; Recovery of Function; Time Factors

This article will review the pathophysiology of postoperative ileus, with emphasis on potential therapeutic targets, and examine the efficacy of pharmacologic and nonpharmacologic interventions. Proposed mechanisms include actuation of spinal and local sympathetic neural reflexes, inflammatory mediation, and exacerbation by anesthetic or surgical procedures. Some procedures or agents have shown clinical benefit, and these include use of laparoscopic surgery, thoracic epidurals, nonsteroidal anti-inflammatory drugs, and opiate antagonists. Other procedures may be helpful with low risk of adverse effects. These include early feeding and ambulation, laxatives, and possibly neostigmine.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Decompression, Surgical; Early Ambulation; Gastrointestinal Motility; Humans; Ileus; Laparoscopy; Naloxone; Narcotic Antagonists; Neostigmine; Piperidines; Postoperative Complications

Surgical management of peritoneal metastases with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is associated with prolonged length of stay and time to return of bowel function. Alvimopan is a peripherally acting opioid antagonist that reduces postoperative ileus. We sought to determine the efficacy of alvimopan on return of bowel function in patients undergoing CRS-HIPEC.. A double-blind, randomized, placebo-controlled, single-institution, IRB-approved trial was conducted in patients undergoing CRS-HIPEC from March 2018 to April 2020. Patients received alvimopan or placebo preoperatively and twice daily postoperatively for 7 days. The primary endpoint (GI-2) was the time of tolerance of solid food and first bowel movement (BM). Secondary endpoints were the proportion of patients with prolonged ileus, time to first flatus, first BM, tolerance of solid food, discharge, and adverse events (AEs).. Sixty-two patients met eligibility criteria and received placebo (n = 32) or alvimopan (n = 30), and were included in the analysis. The median time to GI-2 was 152 hours (95% CI 134, 204) in the placebo arm versus 117 hours (95% CI 102, 158) in the alvimopan arm (p = 0.04). The time to BM was 89 hours (95% CI 71, 114) in the placebo arm vs 67 hours (95% CI 62, 89) in the alvimopan arm (p = 0.02). There were no significant differences in AE rates, proportion of patients with prolonged ileus, or other secondary endpoints.. Perioperative alvimopan was well tolerated and accelerated bowel function recovery in patients undergoing CRS-HIPEC.

Topics: Cytoreduction Surgical Procedures; Humans; Ileus; Narcotic Antagonists; Piperidines

We evaluated the effect of alvimopan treatment vs placebo on health care utilization and costs related to gastrointestinal recovery in patients treated with radical cystectomy in a randomized, phase 4 clinical trial.. Resource utilization data were prospectively collected and evaluated by cost consequence analysis. Hospital costs were estimated from 2012 Medicare reimbursement rates and medication wholesale acquisition costs. Differences in base case mean costs between the study cohorts for total postoperative ileus related costs (hospital days, study drug, nasogastric tubes, postoperative ileus related concomitant medication and postoperative ileus related readmissions) and total combined costs (postoperative ileus related, laboratory, electrocardiograms, nonpostoperative ileus related concomitant medication and nonpostoperative ileus related readmission) were evaluated by probabilistic sensitivity analysis using a bootstrap approach.. Mean hospital stay was 2.63 days shorter for alvimopan than placebo (mean±SD 8.44±3.05 vs 11.07±8.23 days, p=0.005). Use of medications or interventions likely intended to diagnose or manage postoperative ileus was lower for alvimopan than for placebo, eg total parenteral nutrition 10% vs 25% (p=0.001). Postoperative ileus related health care costs were $2,340 lower for alvimopan and mean total combined costs were decreased by $2,640 per patient for alvimopan vs placebo. Analysis using a 10,000-iteration bootstrap approach showed that the mean difference in postoperative ileus related costs (p=0.04) but not total combined costs (p=0.068) was significantly lower for alvimopan than for placebo.. In patients treated with radical cystectomy alvimopan decreased hospitalization cost by reducing the health care services associated with postoperative ileus and decreasing the hospital stay.

Topics: Administration, Oral; Costs and Cost Analysis; Cystectomy; Double-Blind Method; Follow-Up Studies; Gastrointestinal Agents; Hospital Costs; Humans; Ileus; Incidence; Patient Acceptance of Health Care; Piperidines; Postoperative Complications; Prospective Studies; Receptors, Opioid, mu; United States

Radical cystectomy (RC) for bladder cancer is frequently associated with delayed gastrointestinal (GI) recovery that prolongs hospital length of stay (LOS).. To assess the efficacy of alvimopan to accelerate GI recovery after RC.. We conducted a randomized double-blind placebo-controlled trial in patients undergoing RC and receiving postoperative intravenous patient-controlled opioid analgesics.. Oral alvimopan 12 mg (maximum: 15 inpatient doses) versus placebo.. The two-component primary end point was time to upper (first tolerance of solid food) and lower (first bowel movement) GI recovery (GI-2). Time to discharge order written, postoperative LOS, postoperative ileus (POI)-related morbidity, opioid consumption, and adverse events (AEs) were evaluated. An independent adjudication of cardiovascular AEs was performed.. Patients were randomized to alvimopan (n=143) or placebo (n=137); 277 patients were included in the modified intention-to-treat population. The alvimopan cohort experienced quicker GI-2 recovery (5.5 vs 6.8 d; hazard ratio: 1.8; p<0.0001), shorter mean LOS (7.4 vs 10.1 d; p=0.0051), and fewer episodes of POI-related morbidity (8.4% vs 29.1%; p<0.001). The incidence of opioid consumption and AEs or serious AEs (SAEs) was comparable except for POI, which was lower in the alvimopan group (AEs: 7% vs 26%; SAEs: 5% vs 20%, respectively). Cardiovascular AEs occurred in 8.4% (alvimopan) and 15.3% (placebo) of patients (p=0.09). Generalizability may be limited due to the exclusion of epidural analgesia and the inclusion of mostly high-volume centers utilizing open laparotomy.. Alvimopan is a useful addition to a standardized care pathway in patients undergoing RC by accelerating GI recovery and shortening LOS, with a safety profile similar to placebo.. This study examined the effects of alvimopan on bowel recovery in patients undergoing radical cystectomy for bladder cancer. Patients receiving alvimopan experienced quicker bowel recovery and had a shorter hospital stay compared with those who received placebo, with comparable safety.. ClinicalTrials.gov identifier NCT00708201.

Topics: Aged; Analgesics, Opioid; Cardiovascular Diseases; Cystectomy; Defecation; Double-Blind Method; Eating; Female; Gastrointestinal Agents; Gastrointestinal Tract; Humans; Ileus; Length of Stay; Male; Middle Aged; Piperidines; Postoperative Care; Prospective Studies; Recovery of Function; Time Factors

Alvimopan is indicated to accelerate the time to gastrointestinal recovery following partial bowel resection with primary anastomosis. The approved dosing regimen includes an initial dose prior to surgery and 12 mg twice daily after surgery for up to 7 days; however, there are no human studies evaluating the need for the preoperative dose. We report our experience with gastrointestinal recovery when the preoperative dose is omitted.. To evaluate the efficacy of alvimopan therapy when the preoperative dose is not administered.. This retrospective study included elective surgery patients who underwent bowel resection with primary anastomosis without colostomy or ileostomy. The study compared (a) patients who received alvimopan and received a dose preoperatively, (b) patients who received alvimopan but did not receive a dose preoperatively, and (c) matched control patients who did not receive alvimopan. Length of stay following bowel resection, direct hospital costs, time to first bowel movement, and time to oral diet were evaluated.. Of 50 patients who received alvimopan, 27 received the preoperative dose and 23 did not. These 50 patients were matched to similar control patients who received no alvimopan during their admission for resection. Compared with controls, time to discharge was significantly shorter in patients who received alvimopan, regardless of whether the preoperative dose was administered (P < .001) or omitted (P = .03). Patients who did not receive the preoperative dose still experienced faster time to first bowel movement (71 vs 97 hours; P = .006) and faster time to first diet (17 vs 54 hours; P < .001) than non-alvimopan users.. Patients receiving the approved alvimopan dosing regimen experienced the most rapid recovery of gastrointestinal function. However, administering alvimopan only postoperatively (if the preoperative dose is omitted) may still reduce the severity of postoperative ileus.

Topics: Anastomosis, Surgical; Drug Administration Schedule; Female; Gastrointestinal Agents; Humans; Ileus; Intestine, Large; Intestine, Small; Kaplan-Meier Estimate; Length of Stay; Male; Middle Aged; Piperidines; Preoperative Care; Proportional Hazards Models; Retrospective Studies; Treatment Outcome

Alvimopan has been shown to shorten time to return of bowel function (RBF), thereby decreasing length of stay (LOS). The aim of this study was to assess the clinical significance of this effect on actual practice. METJODS: A retrospective and prospective study of elective bowel resection patients was performed. Surgeons were assigned to alvimopan users (treatment) or nonusers (control). Primary outcome measures included LOS, RBF, and total hospital cost (THC).. Mean RBF was 2.93 ± 1.22 days in the treatment group and 4.22 ± 1.81 days in the control group (P < .001). Mean LOS was 7 ± 2.6 days in the treatment group and 7.2 ± 2.2 days in the control group. Mean THC was $7,584 ± $4,770 in the treatment group and $7,310 ± $5,471 in the control group (P > .81). LOS decreased by 2.5 days compared with the historical controls, independent of alvimopan use.. Alvimopan improved RBF but not LOS or THC. Reductions in average LOS of 1 day for ≤6 doses and 2 days if patients received >6 doses were needed to decrease THC.

Topics: Aged; Anastomosis, Surgical; Digestive System Surgical Procedures; Drug Costs; Elective Surgical Procedures; Female; Gastrointestinal Agents; Hospital Costs; Humans; Ileus; Intestines; Length of Stay; Male; Middle Aged; Piperidines; Postoperative Complications; Prospective Studies; Recovery of Function; Retrospective Studies; United States

Alvimopan, a peripherally acting Mu-opioid receptor antagonist, has been shown to enhance recovery of gastrointestinal (GI) function in open bowel resection. The aim of this study was to determine the effect of Alvimopan on patients undergoing laparoscopic right colectomies in preventing postoperative ileus (POI). A prospective, nonrandomized trial of laparoscopic right colectomies was carried out with and without perioperative Alvimopan. The length of stay (LOS), time to first flatus, bowel movement, and tolerance of solid foods were recorded. Additionally, any occurrences of POI defined as the need for insertion of a nasogastric tube (NGT) were also noted. Student t tests were used for statistical analysis. A total of 33 patients underwent laparoscopic right colectomies for both benign and malignant diseases from October 2008, to December 2009. Sixteen patients received Alvimopan, whereas 17 patients did not. The demographics of both patient groups were similar. Patients receiving Alvimopan had an accelerated return of bowel function in terms of first flatus (2.37 vs 3.34; P = 0.03), tolerance of solid food (2.75 vs 3.94; P = 0.03), and first stool (2.53 vs 3.80; P = 0.04). There was a trend toward shorter LOS in patients receiving Alvimopan (P = 0.07). Two patients with POI requiring NGT did not receive Alvimopan. Alvimopan was successful in enhancing return of GI function in laparoscopic right colectomies and avoiding POI. The decreased LOS trended but did not approach statistical significance. A large randomized prospective trial will be needed to determine the validity of this study.

Topics: Administration, Oral; Aged; Colectomy; Colonic Diseases; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Ileus; Laparoscopy; Male; Piperidines; Postoperative Complications; Prospective Studies; Receptors, Opioid, mu; Recovery of Function; Treatment Outcome

A pooled post hoc responder analysis was performed to assess the clinical benefit of alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist, for the management of postoperative ileus after bowel resection.. Adult patients who underwent laparotomy for bowel resection scheduled for opioid-based intravenous patient-controlled analgesia received oral alvimopan or placebo preoperatively and twice daily postoperatively until hospital discharge or for 7 postoperative days. The proportion of responders and numbers needed to treat (NNT) were examined on postoperative days (POD) 3-8 for GI-2 recovery (first bowel movement, toleration of solid food) and hospital discharge order (DCO) written.. Alvimopan significantly increased the proportion of patients with GI-2 recovery and DCO written by each POD (P < 0.001 for all). More patients who received alvimopan achieved GI-2 recovery on or before POD 5 (alvimopan, 80%; placebo, 66%) and DCO written before POD 7 (alvimopan, 87%; placebo, 72%), with corresponding NNTs equal to 7.. On each POD analyzed, alvimopan significantly increased the proportion of patients who achieved GI-2 recovery and DCO written versus placebo and was associated with relatively low NNTs. The results of these analyses provide additional characterization and support for the overall clinical benefit of alvimopan in patients undergoing bowel resection.

Topics: Aged; Colonic Neoplasms; Digestive System Surgical Procedures; Diverticulosis, Colonic; Female; Humans; Ileus; Intestines; Length of Stay; Male; Middle Aged; Piperidines; Postoperative Complications; Receptors, Opioid, mu; Recovery of Function; Rectal Neoplasms; Treatment Outcome

Alvimopan has received Food and Drug Administration approval to accelerate the time to upper and lower gastrointestinal recovery following partial large or small bowel resection with primary anastomosis.. To assess the efficacy, safety, and economic benefit of alvimopan in patients undergoing open or laparoscopic bowel resection in a community hospital system setting.. This 6-month, open-label, multi-hospital, prospective study combined with a retrospective chart review compared postoperative length of stay and postoperative ileus-related morbidity (nasogastric tube insertion, hospital readmission) for patients undergoing open or laparoscopic bowel resection who received alvimopan 12 mg (n = 108) versus historical control bowel resection patients (n = 91) who would have been eligible to receive alvimopan. Multivariate analysis assessed the effects of age and surgery type on postoperative length of stay. Additional-day hospital costs were estimated using ordinary least-squares regression to calculate costs based on length of stay in the control cohort.. Compared with historical controls, patients receiving alvimopan had a mean 1.8-day shorter postoperative length of stay (p = 0.01) and lower rates of nasogastric tube insertion (2% vs 15%, p < 0.001). Multivariate analysis revealed a statistically significant reduction in postoperative length of stay in the alvimopan group of approximately 1.2 days (p = 0.01), regardless of age or surgery type, with an even larger difference (3.2 days) observed in patients ≥70 years old. Mean cost savings associated with alvimopan use ranged from $531 (laparoscopic bowel resection) to $997 (open bowel resection) per patient.. Consistent with clinical trial data, alvimopan use resulted in an approximately 1 day shorter postoperative length of stay and was associated with substantial cost savings.

Topics: Age Factors; Aged; Anastomosis, Surgical; Cost Savings; Digestive System Surgical Procedures; Female; Gastrointestinal Agents; Hospitals, Community; Humans; Ileus; Intubation, Gastrointestinal; Laparoscopy; Least-Squares Analysis; Length of Stay; Male; Middle Aged; Multivariate Analysis; Piperidines; Postoperative Complications; Prospective Studies; Recovery of Function; Retrospective Studies

To investigate the efficacy and safety of alvimopan, 12 mg, administered orally 30 to 90 minutes preoperatively and twice daily postoperatively in conjunction with a standardized accelerated postoperative care pathway for managing postoperative ileus after bowel resection.. This multicenter, randomized, placebo-controlled, double-blind, phase 3 trial enrolled adult patients undergoing partial bowel resection with primary anastomosis by laparotomy and scheduled to receive intravenous, opioid-based, patient-controlled analgesia. A standardized accelerated postoperative care pathway including early ambulation, oral feeding, and postoperative nasogastric tube removal was used to facilitate gastrointestinal (GI) tract recovery in all of the patients.. The primary end point was time to GI-2 recovery (toleration of solid food and first bowel movement). Secondary end points included time to GI-3 recovery (toleration of solid food and first flatus or bowel movement), hospital discharge order written, and actual hospital discharge. Postoperative length of hospital stay based on calendar day of hospital discharge order written, opioid consumption, and overall postoperative ileus-related morbidity were recorded.. Alvimopan, 12 mg, was well tolerated and significantly accelerated GI-2 recovery, GI-3 recovery, and actual hospital discharge compared with a standardized accelerated postoperative care pathway alone (hazard ratio = 1.5, 1.5, and 1.4, respectively; P < .001 for all). Time to hospital discharge order written as measured by hazard ratio (1.4) and by postoperative calendar days (mean for alvimopan, 5.2 days; mean for placebo, 6.2 days) was also accelerated. Opioid consumption was comparable between groups, and alvimopan was associated with reduced postoperative ileus-related morbidity compared with placebo.. Alvimopan, 12 mg, administered 30 to 90 minutes before and twice daily after bowel resection is well tolerated, accelerates GI tract recovery, and reduces postoperative ileus-related morbidity without compromising opioid analgesia.

Topics: Adult; Critical Pathways; Double-Blind Method; Drug Administration Schedule; Female; Gastrointestinal Motility; Humans; Ileus; Intestines; Male; Middle Aged; Piperidines; Postoperative Care; Postoperative Complications; Recovery of Function; Treatment Outcome

Post-operative ileus (POI) affects most patients undergoing abdominal surgery.. To evaluate the effect of alvimopan, a peripherally acting mu-opioid receptor antagonist, on POI by negating the impact of opioids on gastrointestinal (GI) motility without affecting analgesia in patients outside North America.. Adult subjects undergoing open abdominal surgery (n = 911) randomly received oral alvimopan 6 or 12 mg, or placebo, 2 h before, and twice daily following surgery. Opioids were administered as intravenous patient-controlled analgesia (PCA) or bolus injection. Time to recovery of GI function was assessed principally using composite endpoints in subjects undergoing bowel resection (n = 738).. A nonsignificant reduction in mean time to tolerate solid food and either first flatus or bowel movement (primary endpoint) was observed for both alvimopan 6 and 12 mg; 8.5 h (95% CI: 0.9, 16.0) and 4.8 h (95% CI: -3.2, 12.8), respectively. However, an exploratory post hoc analysis showed that alvimopan was more effective in the PCA (n = 317) group than in the non-PCA (n = 318) group. Alvimopan was well tolerated and did not reverse analgesia.. Although the significant clinical effect of alvimopan on reducing POI observed in previous trials was not reproduced, this trial suggests potential benefit in bowel resection patients who received PCA.

Topics: Aged; Defecation; Dose-Response Relationship, Drug; Double-Blind Method; Female; Gastrointestinal Motility; Humans; Ileus; Male; Middle Aged; Narcotic Antagonists; Pain Measurement; Piperidines; Postoperative Complications; Stomach Diseases; Treatment Outcome

Postoperative ileus (POI), an interruption of coordinated bowel motility after operation, is exacerbated by opioids used to manage pain. Alvimopan, a peripherally acting mu-opioid receptor antagonist, accelerated gastrointestinal (GI) recovery after bowel resection in randomized, double-blind, placebo-controlled, multicenter phase III POI trials. The effect of alvimopan on POI-related morbidity for patients who underwent bowel resection was evaluated in a post-hoc analysis.. Incidence of POI-related postoperative morbidity (postoperative nasogastric tube insertion or POI-related prolonged hospital stay or readmission) was analyzed in four North American trials for placebo or alvimopan 12 mg administered 30 minutes or more preoperatively and twice daily postoperatively until hospital discharge (7 or fewer postoperative days). GI-related adverse events and opioid consumption were summarized for each treatment. Estimations of odds ratios of alvimopan to placebo and number needed to treat (NNT) to prevent one patient from experiencing an event of POI-related morbidity were derived from the analysis.. Patients receiving alvimopan 12 mg were less likely to experience POI-related morbidity than patients receiving placebo (odds ratio = 0.44, p < 0.001). Fewer patients receiving alvimopan (alvimopan, 7.6%; placebo, 15.8%; NNT = 12) experienced POI-related morbidity. There was a lower incidence of postoperative nasogastric tube insertion, and other GI-related adverse events on postoperative days 3 to 6 in the alvimopan group than the placebo group. Opioid consumption was comparable between groups.. Alvimopan 12 mg was associated with reduced POI-related morbidity compared with placebo, without compromising opioid-based analgesia in patients undergoing bowel resection. Relatively low NNTs are clinically meaningful and reinforce the potential benefits of alvimopan for the patient and health care system.

Topics: Digestive System Surgical Procedures; Double-Blind Method; Female; Gastrointestinal Agents; Humans; Ileus; Male; Middle Aged; Piperidines; Postoperative Complications; Receptors, Opioid, mu

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.

Topics: Abdomen; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Double-Blind Method; Female; Gastrointestinal Tract; Humans; Hysterectomy; Ileus; Laparotomy; Male; Middle Aged; Pain Measurement; Pain, Postoperative; Pelvis; Piperidines; Proportional Hazards Models; Receptors, Opioid, mu; Recovery of Function; Survival Analysis; Treatment Outcome

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.

Topics: Adult; Aged; Aged, 80 and over; Colectomy; Double-Blind Method; Eating; Female; Follow-Up Studies; Gastrointestinal Motility; Humans; Hysterectomy; Ileus; Length of Stay; Male; Middle Aged; Piperidines; Receptors, Opioid, mu; Recovery of Function; United States

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.

Topics: Adult; Aged; Aged, 80 and over; Defecation; Double-Blind Method; Female; Gastrointestinal Agents; Humans; Hysterectomy; Ileus; Intestine, Large; Intestine, Small; Laparotomy; Male; Middle Aged; Patient Discharge; Piperidines; Placebos; Postoperative Complications; Premedication; Receptors, Opioid, mu; Recovery of Function; Time Factors

Post-operative ileus and delayed return of gastrointestinal function are complications seen frequently in patients undergoing colorectal surgery. Many enhanced recovery after surgery protocols include alvimopan to inhibit the effects of opiates in the gastrointestinal tract and lidocaine to augment analgesics. Limited data exist regarding alvimopan's efficacy in opiate-sparing regimens.. This single-center, retrospective cohort analysis was conducted in a randomly selected population of adult patients undergoing colorectal resection between February 2018 and October 2019. Patients meeting inclusion criteria were divided into four groups dependent upon whether or not they received alvimopan (A or a) and/or lidocaine (L or l). The primary endpoint in this study was median time to first bowel movement or discharge, whichever came first. Our secondary endpoint was length of stay.. Of the 430 patients evaluated, a total of 192 patients were included in the final evaluation in the following groups: AL (n = 93), Al (n = 34), aL (n = 44), and al (n = 21). A significant difference was found among the groups for the primary outcome of median time to bowel movement or discharge (p = 0.001). Three subsequent pair-wise comparisons resulted in a significant difference in the primary outcome: group AL 39.4 h vs. group aL 54.0 h (p = 0.003), group AL 39.4 h vs. group al 55.4 h (p = 0.001), and group Al 44.9 h vs. group al 55.4 h (p = 0.01). Length of stay was significantly reduced by 1.8 days in groups AL and Al compared to group aL (p < 0.001).. Treatment with alvimopan resulted in a significant improvement in time to GI recovery and decreased length of stay in an established ERAS program. While lidocaine's reduction in opiates was minimal, the group receiving both alvimopan and lidocaine had the greatest reduction in time to GI recovery and length of stay.

Topics: Adult; Colorectal Surgery; Gastrointestinal Agents; Humans; Ileus; Length of Stay; Lidocaine; Opiate Alkaloids; Piperidines; Postoperative Complications; Recovery of Function; Retrospective Studies

The use of alvimopan at the time of cystectomy has been associated with improved perioperative outcomes. Naloxegol is a less costly alternative that has been used in some centers. This study aims to compare the perioperative outcomes of patients undergoing cystectomy with urinary diversion who receive the mu-opioid antagonist alvimopan versus naloxegol.. This was a retrospective review that included all patients who underwent cystectomy with urinary diversion at our institution between 2007-2020. Comparisons were made between patients who received perioperative alvimopan, naloxegol and no mu-opioid antagonist (controls).. In 715 patients who underwent cystectomy, 335 received a perioperative mu-opioid antagonist, of whom 57 received naloxegol. Control patients, compared to naloxegol and alvimopan patients, experienced a significantly (p < 0.05) delayed return of bowel function (4.3 vs. 2.5 vs. 3.0 days) and longer hospital length of stay (7.9 vs. 7.5 vs. 6.5 days), respectively. The incidence of nasogastric tube use (14.2% vs. 12.5% vs. 6.5%) and postoperative ileus (21.6% vs. 21.1% vs. 13.3%) was also most common in the control group compared to the naloxegol and alvimopan cohorts, respectively. A multivariable analysis revealed that when comparing naloxegol and alvimopan, there was no difference in return of bowel function (OR 0.88, p = 0.17), incidence of postoperative ileus (OR 1.60, p = 0.44), or hospital readmission (OR 1.22, p = 0.63).. Naloxegol expedites the return of bowel function to the same degree as alvimopan in cystectomy patients. Given the lower cost of naloxegol, this agent may be a preferable alternative to alvimopan.

Topics: Cystectomy; Gastrointestinal Agents; Humans; Ileus; Length of Stay; Morphinans; Narcotic Antagonists; Piperidines; Polyethylene Glycols; Postoperative Complications; Urinary Diversion

Postoperative ileus (POI) is a temporary delay of coordinated intestinal peristalsis. Alvimopan, an oral peripherally acting mu-opioid receptor antagonist approved for accelerating gastrointestinal recovery, has never been studied specifically in patients with inflammatory bowel disease (IBD).. To investigate the efficacy of alvimopan in preventing POI among IBD patients.. A retrospective chart review was conducted on 246 IBD patients undergoing bowel surgery between 2012 and 2017. Data collected included demographics, IBD subtype, length of stay (LOS), postoperative gastrointestinal symptoms, and administration of alvimopan. The primary outcome was POI; secondary gastrointestinal recovery outcomes were: time to first flatus, time to first bowel movement, time to tolerating a liquid diet, time to tolerating solid food, and LOS.. When compared with the control group, patients in the alvimopan group had shorter times to tolerating liquids and solids, first flatus, and first bowel movements (p < 0.01). LOS was shorter in the alvimopan group when compared with controls (p < 0.01). The overall incidence of POI was higher in controls than in the alvimopan group (p = 0.07). For laparoscopic surgeries, the incidence of POI was also higher in controls than in the alvimopan group (p < 0.01). On multivariable analysis, alvimopan significantly decreased time to all gastrointestinal recovery endpoints when compared to controls (p < 0.01).. Alvimopan is effective in accelerating time to gastrointestinal recovery and reducing POI in IBD patients. While the benefits of alvimopan have been demonstrated previously, this is the first study of the efficacy of alvimopan in IBD patients.

Topics: Adult; Female; Gastrointestinal Agents; Humans; Ileus; Inflammatory Bowel Diseases; Male; Middle Aged; Piperidines; Postoperative Complications; Retrospective Studies

To evaluate the impact of alvimopan in patient undergoing radical cystectomy (RC) for bladder cancer. We hypothesize that alvimopan can decrease cost for RC by reducing length of stay (LOS).. We identified patients who underwent elective RC for bladder cancer from 2009 to 2015 in the Premier Healthcare Database, a nationwide, all-payer hospital-based database, and compared patients who received and did not receive alvimopan in the perioperative period. Hospitals that had no record of administering alvimopan for patients undergoing RC were excluded. The primary outcomes were LOS and the direct hospital costs. The secondary outcomes were 90-day readmission for ileus and major complications.. After applying the inclusion criteria, the study cohort consisted of 1087 patients with 511 patients receiving perioperative alvimopan. Alvimopan was associated with a reduction in hospital costs by -$2709 (95% confidence interval: -$4507 to -$912, P = .003), decreased median LOS (7 vs 8 days, P < .001), and lower likelihood of readmission for ileus (adjusted odds ratio: 0.63, P = .041). While alvimopan use led to higher pharmacy costs, this was outweighed by lower room and board costs due to the reduced LOS. There was no significant difference between 2 groups regarding major complications. These results were robust across multiple adjusted regression models.. Our data show that alvimopan is associated with a substantial cost-saving in patients undergoing RC, and suggest that routine use of alvimopan may be a potential cost-effective strategy to reduce the overall financial burden of bladder cancer.

Topics: Aged; Cost-Benefit Analysis; Cystectomy; Female; Gastrointestinal Agents; Hospital Costs; Humans; Ileus; Length of Stay; Lower Gastrointestinal Tract; Male; Neoplasm Staging; Piperidines; Postoperative Complications; Recovery of Function; Retrospective Studies; United States; Urinary Bladder Neoplasms

The development of enhanced recovery after surgery (ERAS) protocols for patients undergoing radical cystectomy (RC) represents a significant advance in perioperative care.. To evaluate gastrointestinal (GI) complications following RC and urinary diversion (UD) using our institutional ERAS protocol.. We identified 377 consecutive cases of open RC and UD for which our ERAS protocol was used from May 2012 to December 2015. Exclusion criteria were consent refusal; non-bladder primary disease; palliative, salvage, or additional surgery; and prolonged postoperative intubation. A matched cohort of 144 patients for whom a traditional postoperative protocol (pre-ERAS) was used between 2003 and 2012 was selected for comparison.. A total of 292 ERAS patients with median age of 70 yr were included in the study, 65% of whom received an orthotopic neobladder. The median time to first flatus and bowel movement was 2 d. The median length of stay was 4 d. GI complications occurred in 45 patients (15.4%) during the first 30 d following RC, 93% of which were of minor grade. The most common GI complication was postoperative ileus (POI) in 34 cases (11.6%). Some 22 patients (7.5%) required a nasogastric tube, and parenteral nutrition was required in three patients. The rate of 30-d GI complications was significantly lower in the ERAS cohort than in the control group (13% vs 27%; p=0.003), as was the rate of POI (7% vs 23%; p<0.001). This effect was independent of other variables (hazard ratio 0.38, 95% confidence interval 0.18-0.82; p=0.01).. Our institutional ERAS protocol for RC is associated with significantly improved perioperative GI recovery and lower rates of GI complications. This protocol can be tested in multi-institutional studies to reduce GI morbidity associated with RC.. In this study, we showed that an enhanced recovery protocol for patients undergoing radical cystectomy for bladder cancer was associated with a significantly shorter length of hospital stay and lower rates of gastrointestinal complications, especially postoperative ileus.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Carcinoma, Transitional Cell; Case-Control Studies; Clinical Protocols; Cystectomy; Dehydration; Female; Gastrointestinal Agents; Gastrointestinal Diseases; Humans; Ileus; Intubation, Gastrointestinal; Length of Stay; Male; Middle Aged; Parenteral Nutrition; Perioperative Care; Piperidines; Postoperative Complications; Proportional Hazards Models; Urinary Bladder Neoplasms; Urinary Diversion; Urinary Tract Infections

Topics: Cystectomy; Defecation; Humans; Ileus; Piperidines

Previous analyses evaluating alvimopan included patients at varying risk for ileus after intestinal resection, which may have precluded its widespread adoption. We assess the early and delayed effects of alvimopan in patients stratified by risk for ileus after intestinal and colon resection.. From the Premier Perspective database, patients with elective small and large bowel resections from 2012 to 2014 were identified. Multivariable analysis identified 14 perioperative risk factors for postoperative ileus. Within low- (0-4 factors), intermediate- (5 factors), and high-risk (6-12 factors) ileus categories, alvimopan and no-alvimopan patients were propensity-score matched for demographics, morbidities, diagnosis, surgery and approach, postoperative complications, surgeon specialty, and hospital features. In-hospital postoperative ileus, length of stay, discharge destination, and ileus-related readmission were compared.. Of 52,948 patients, 15,719 (29.7%) received alvimopan. Risk for ileus in low- (18,784), intermediate- (14,370), and high-risk (19,794) categories was 8.9, 13, and 22% (p ≤ .0001) respectively. After matching, alvimopan was associated with significantly reduced in-hospital postoperative ileus in all (low, 6%; intermediate, 9.4%; and high risk, 16.2%) categories. Hospital stay and 30-, 60-, and 90-day postdischarge ileus were also significantly lower with alvimopan. For low-risk patients, alvimopan increased discharge to home, while 90-day emergency readmission was reduced.. Alvimopan, regardless of ileus risk, improves ileus, hospital stay, and ileus-related readmission after intestinal resection and these effects are sustained over the long term. Since fewer than a third of patients currently receive alvimopan, its routine adoption with small and large intestinal resection will significantly impact patients and health systems.

Topics: Colectomy; Digestive System Surgical Procedures; Female; Gastrointestinal Agents; Humans; Ileus; Intestines; Length of Stay; Male; Patient Readmission; Piperidines; Risk Factors

Opioid analgesics exacerbate ileus through peripheral μ-opioid receptor action. Alvimopan, a μ-opioid receptor antagonist, has been proposed to alleviate postoperative ileus, leading to decreased time to return of gastrointestinal function and hospital discharge. As opioid-induced motility issues are only one factor affecting postoperative ileus, continued examination of the cost of the use and efficacy of the drug is needed. Data for this study were collected retrospectively from the charts of 55 patients who received an anastomosis and were given alvimopan at Morristown Medical Center between 2010 and 2013 as well as from 58 appropriately matched controls. The billing record and chart for each patient was examined, and information on total hospital charges, age, sex, body mas index, primary diagnosis, procedure type, length of stay (days), time to return of bowel function (hours), and outcomes were recorded for analysis. No difference between patients given alvimopan and controls was observed for the length of hospital stay (4.6 vs 4.8 days) or for time to return of bowel function (68.5 vs 67.3 hours). Total hospital charges were higher for treated patients (p=0.0080), averaging $48 705.15 and $41 068.80, respectively. Alvimopan was not associated with improved clinical outcome but was associated with an increase in hospital charges within this population.

Topics: Aged; Body Mass Index; Female; Gastrointestinal Diseases; Health Care Costs; Humans; Ileus; Length of Stay; Male; Middle Aged; Piperidines; Postoperative Complications; Postoperative Period; Receptors, Opioid, mu; Retrospective Studies; Treatment Outcome

Topics: Colorectal Surgery; Digestive System Surgical Procedures; Gastrointestinal Agents; Humans; Ileus; Piperidines; Recovery of Function

Topics: Colorectal Surgery; Cost Savings; Digestive System Surgical Procedures; Humans; Ileus; Piperidines

Alvimopan has decreased ileus and need for nasogastric tube (NGT) after radical cystectomy (RC). However, the natural history of ileus versus intestinal obstruction in patients receiving alvimopan is not well defined. We sought to examine the implications of NGT placement before and after the introduction of alvimopan for RC patients.. Retrospective review identified 278 and 293 consecutive patients who underwent RC before and after instituting alvimopan between June 2009 and May 2014. Baseline characteristics and postoperative outcomes were compared by alvimopan status. Multivariate logistic regression was performed to assess the impact of alvimopan on rates of NGT placement and reoperation for bowel complications.. The cohorts had similar age, stage, approach, and BMI. Patients receiving alvimopan had decreased ileus (16 vs 32 %, p < 0.01) but similar rates of reoperation for bowel complications (2.8 vs 2.7 %). On multivariate analysis, alvimopan was associated with lower risk of NGT placement (OR 0.30, p < 0.01). For patients requiring NGT placement, there was an increased rate of reoperation among patients receiving alvimopan compared with those who did not (28 vs 11 %, p = 0.03). Patients receiving alvimopan who needed NGT had significantly increased median length of stay (22 vs 7 days), need for TPN (66 vs 5.3 %), and readmission for ileus (10.3 vs 2.3 %) compared with those who did not require NGT.. Alvimopan significantly reduced the incidence of ileus and NGT placement following RC. NGT placement was associated with an increased need for reoperation for bowel complications in the setting of alvimopan.

Topics: Aged; Carcinoma, Transitional Cell; Cystectomy; Female; Gastrointestinal Agents; Humans; Ileus; Intubation, Gastrointestinal; Logistic Models; Male; Middle Aged; Multivariate Analysis; Piperidines; Postoperative Care; Postoperative Complications; Reoperation; Retrospective Studies; Urinary Bladder Neoplasms; Urinary Diversion

Postoperative ileus (POI) is a major cause of morbidity, increased length of stay (LOS) and hospital cost after colorectal surgery. Alvimopan is a µ-opioid antagonist used to accelerate upper and lower gastrointestinal function after bowel resection. We hypothesized that alvimopan would reduce LOS in patients undergoing colorectal resection with stoma, a situation that has not been evaluated.. A retrospective review (2010-2015) identified 58 patients who underwent colorectal resection for benign or malignant disease with stoma creation and received alvimopan. They were case-matched to 58 non-alvimopan patients based on age, BMI, baseline comorbidities, stoma type created and surgical approach. We compared overall LOS, incidence of POI and other postoperative complications.. There were equal numbers of laparoscopic (N = 18) and open resections (N = 40) in the alvimopan group and non-alvimopan group. There were also equal numbers of patients with an ileostomy (N = 37) or colostomy (N = 21) in each group. Overall, 41 patients underwent resection for malignant disease in the alvimopan group compared to 37 in the non-alvimopan group. There was a significant reduction in median LOS overall (alvimopan 5 (4-7) versus control 6 (4.75-9.25) days, P = 0.03). While the 6-day median LOS was similar for patients undergoing ileostomy creation (P = 0.25), alvimopan patients had a 3-day decreased median LOS that approached statistical significance (P = 0.06). The overall 30-day complication rate was higher in the control group (41.4 vs. 51.7%, P = 0.26), but the readmission rate within 30 days was higher in the alvimopan group (19 vs. 13.8%, P = 0.45). Neither of these differences reached statistically significance.. The use of alvimopan in patients undergoing colorectal resection with stoma is associated with a significantly shorter LOS, but the increased readmission rate warrants further study. Based on these data, alvimopan should be evaluated in a controlled setting for patients undergoing colorectal resection with colostomy creation.

Topics: Adult; Aged; Colectomy; Colonic Diseases; Female; Gastrointestinal Agents; Humans; Ileus; Length of Stay; Male; Middle Aged; Ostomy; Piperidines; Postoperative Complications; Rectal Diseases; Rectum; Retrospective Studies; Treatment Outcome

To examine the impact of alvimopan on outcomes and costs in a rigorous enhanced recovery colorectal surgery protocol.. Postoperative ileus remains a major source of morbidity and costs in colorectal surgery. Alvimopan has been shown to reduce incidence of postoperative ileus in enhanced recovery colorectal surgery; however, data are equivocal regarding its benefit in reducing length of stay and costs.. Patients undergoing major elective enhanced recovery colorectal surgery were identified from a prospectively-collected database (2010-2013). Multivariable analyses were employed to compare outcomes and hospital costs among patients who had alvimopan versus no alvimopan by adjusting for demographic, clinical, and treatment characteristics.. A total of 660 patients were included; 197 patients received alvimopan and 463 patients had no alvimopan. In unadjusted analysis, the alvimopan group had a faster return of bowel function, shorter length of stay, and lower rates of ileus, Foley re-insertion, and urinary tract infection (all P < 0.01). After adjustment, alvimopan was associated with a faster return of bowel function by 0.6 day (P = 0.0006), and lower incidence of postoperative ileus (odds ratio 0.23, P = 0.0002). With adjustment, alvimopan was associated with a shorter length of stay by 1.6 days (P = 0.002), and a hospital cost savings of $1492 per patient (P = 0.01).. Alvimopan administration as an element of enhanced recovery colorectal surgery is associated with faster return of bowel function, lower incidence of postoperative ileus, shorter hospitalization, and a significant cost savings. These results suggest that alvimopan is cost-effective in the setting of enhanced recovery colorectal surgery protocols, and should therefore be considered in these programs.

Topics: Adult; Aged; Body Mass Index; Colorectal Surgery; Cost Savings; Cost-Benefit Analysis; Female; Gastrointestinal Agents; Hospital Costs; Humans; Ileus; Laparoscopy; Length of Stay; Male; Middle Aged; Piperidines; Prospective Studies; Recovery of Function; Risk Factors; United States

Alvimopan's goal is to minimize postoperative ileus and optimize outcomes; however, evidence in laparoscopic surgery is lacking. Our goal was to evaluate the benefit of alvimopan in laparoscopic colorectal surgery with an enhanced recovery pathway (ERP).. Laparoscopic colorectal cases were stratified into alvimopan and control cohorts, then case-matched for comparability. All followed an identical ERP. The main outcomes were length of stay, complications, readmissions, and costs in the alvimopan and control groups.. About 321 patients were analyzed in each cohort. Operative times were comparable (P = .08). Postoperatively, complication rates were similar (P = .29), with no difference in ileus (P = 1.00). The length of stay (3.69 vs 3.49 days; P = .16), readmission (2.8% vs 3.7%; P = .66) and reoperation rates (2.2% vs 1.6%; P = .77) were comparable for alvimopan and controls, respectively. Total costs were similar ($14,932.47 alvimopan vs $14,846.56 controls; P = .90), but the additional costs in the alvimopan group could translate to savings of $27,577 in the cohort.. Alvimopan added no benefit in patient outcomes in laparoscopic colorectal surgery with an ERP. These results could drive a change in current practice. Controlled studies are warranted to define the cost and/or benefit in clinical practice.

Topics: Aged; Colorectal Surgery; Cost-Benefit Analysis; Databases, Factual; Elective Surgical Procedures; Female; Follow-Up Studies; Gastrointestinal Agents; Humans; Ileus; Laparoscopy; Male; Middle Aged; Minimally Invasive Surgical Procedures; Piperidines; Postoperative Complications; Recovery of Function; Reference Values; Retrospective Studies; Risk Assessment; Statistics, Nonparametric; Treatment Outcome

Topics: Gastrointestinal Agents; Humans; Ileus; Piperidines; Postoperative Complications

Alvimopan is an US-FDA approved, peripherally acting mu opioid receptor antagonist which when started pre-operatively has been shown to hasten intestinal motility and reduce the duration of post-operative ileus. However the logistics involved in procuring, storing and dispensing the drug and the cost of the drug for fifteen doses as approved by FDA prohibits the use of it on a regular basis.

Topics: Humans; Ileus; Piperidines; Postoperative Complications; Receptors, Opioid, mu

Topics: Cystectomy; Female; Gastrointestinal Agents; Gastrointestinal Tract; Humans; Ileus; Male; Piperidines; Recovery of Function

Topics: Cystectomy; Female; Gastrointestinal Agents; Gastrointestinal Tract; Humans; Ileus; Male; Piperidines; Recovery of Function

Topics: Analgesia, Epidural; Digestive System Surgical Procedures; Gastrointestinal Agents; Humans; Ileus; Intestines; Piperidines; Postoperative Complications

Topics: Cystectomy; Female; Gastrointestinal Agents; Gastrointestinal Tract; Humans; Ileus; Male; Piperidines; Recovery of Function

Topics: Cystectomy; Female; Gastrointestinal Agents; Gastrointestinal Tract; Humans; Ileus; Male; Piperidines; Recovery of Function

Radical cystectomy is associated with significant morbidity and cost, with rates of gastrointestinal complications as high as 30%. Alvimopan is a mu opioid receptor antagonist that has been shown in randomized-control trials to accelerate gastrointestinal recovery in patients undergoing bowel resection with primary anastamosis. We report our experience with gastrointestinal recovery for patients undergoing cystectomy with urinary diversion treated with alvimopan and cost benefit associated.. Between January 2008 and October 2012, 80 patients underwent radical cystectomy with urinary diversion at two institutions. Forty-two patients in our study did not receive alvimopan preoperatively. Thirty-eight patients received perioperative alvimopan and were without postoperative nasogastric decompression. Return of bowel function, initiation of diet, and gastrointestinal complications and estimated cost of hospitalization were evaluated.. Times to first flatus (3.1 days versus 4.7 days, p < 0.01, 95% CI 0.96-2.24) and bowel movement (3.9 days versus 4.9 days, p < 0.01, 95% CI 0.45-1.55) were significantly shorter in those patients who received alvimopan. Additionally, the initiation of clear liquid diet (4.1 days versus 5.5 days, p < 0.01, 95% CI 0.70-2.10), regular diet (5.2 days versus 6.3 days, p < 0.01, 95% CI 0.39-1.81) and hospital discharge (6.1 days versus 7.7 days, p = 0.04, 95% CI 0.01-3.21) were accelerated in the alvimopan cohort. There were no incidences of prolonged ileus in patients who received perioperative alvimopan (0% versus 26.2%, p < 0.01). With an approximate average cost of alvimopan administration $825 per hospitalization, the average cost benefit of administration over control was $1515 per hospitalization. The cost benefit was mainly a result of a shorter inpatient hospitalization and lack of gastrointestinal morbidity which accumulated a majority of the difference.. In our experience, the use of alvimopan perioperatively significantly accelerates the rate of gastrointestinal recovery and hospital discharge, eliminates the need for nasogastric tube decompression, and reduces the incidence of post-operative ileus in patients following radical cystectomy and urinary diversion.

Topics: Aged; Cost-Benefit Analysis; Cystectomy; Female; Gastrointestinal Agents; Gastrointestinal Tract; Humans; Ileus; Incidence; Male; Perioperative Period; Piperidines; Receptors, Opioid, mu; Recovery of Function; Retrospective Studies; Time Factors; Treatment Outcome; Urinary Diversion

Off-label uses of the peripheral μ-opioid receptor antagonists alvimopan and methylnaltrexone are reviewed.. Alvimopan is approved by the Food and Drug Administration (FDA) for postoperative ileus after surgeries that include partial bowel resection with primary anastomosis, while methylnaltrexone is approved for the treatment of opioid-induced constipation (OIC) in patients with advanced illness who are receiving palliative care. Literature describing the off-label use of alvimopan in the treatment of OIC and of methylnaltrexone in postoperative ileus was reviewed and included retrospective studies and prospective Phase II-IV trials. Randomized controlled trials did not demonstrate consistent benefit of alvimopan in OIC nor of methylnaltrexone in postoperative ileus. A greater proportion of patients receiving alvimopan for OIC experienced severe adverse cardiovascular events, leading to a risk evaluation and mitigation strategy and discontinuation of its study in this condition. Data are limited and unreplicated for the off-label use of alvimopan for postoperative ileus in patients undergoing abdominal hysterectomy. Individual studies suggest benefit with methylnaltrexone for OIC in unlabeled populations, including patients with non-cancer-related pain, opioid dependence, opioid sedation, and opioid use after orthopedic surgery; however, confirmatory evaluations have not been performed.. Trials of alvimopan in the FDA-approved use of methylnaltrexone (OIC) indicate potentially serious cardiovascular safety concerns and conflicting findings of efficacy. Similarly, trials of methylnaltrexone in the FDA-approved use of alvimopan (postoperative ileus) consistently showed no benefit. Evaluations of both drugs in their labeled conditions in populations not endorsed in their product labeling have been limited and largely unreplicated.

Topics: Analgesics, Opioid; Constipation; Gastrointestinal Agents; Humans; Ileus; Naltrexone; Narcotic Antagonists; Off-Label Use; Piperidines; Postoperative Complications; Quaternary Ammonium Compounds

Topics: Humans; Ileus; Piperidines; Postoperative Complications

Alvimopan was approved by the Food and Drug Administration in May 2008 and has been shown to accelerate gastrointestinal recovery after colectomy. Our independent study evaluated alvimopan as it is used in actual hospital practice in the state of Michigan. We hypothesized that alvimopan significantly decreases incidence of prolonged ileus and reduces length of stay (LOS) in patients who have undergone colectomy.. We identified 4749 patients from the Michigan Surgical Quality Collaborative (N = 28 hospitals) database between August 2007 and December 2010 who underwent elective colectomy operations. A total of 528 patients received alvimopan both pre- and postoperatively. We first selected a control group of patients from hospitals that had never administered alvimopan (n = 1833) and used propensity matching to manage differences in patient demographics and clinical characteristics. To control for hospital and surgeon characteristics, we then performed a sensitivity analysis, using a separate group of historical control patients treated before May 2008 in hospitals that would later administer alvimopan (n = 270). The Fisher exact test was used to compare complication rates, and the Student t test was used to compare LOS.. Patients who received alvimopan had significantly lower incidence of prolonged ileus (2.3% vs 7.9%; P < 0.001) and a significantly shorter LOS (4.84 ± 4.54 vs 6.40 ± 4.45 days; P < 0.001) than control patients in hospitals that had never administered alvimopan. No differences were noted in these outcomes using sensitivity analysis.. This study suggests that the actual utilization of alvimopan leads to a reduction in prolonged ileus and LOS in patients who underwent colectomy. By accelerating postoperative recovery, alvimopan has the potential to benefit patients and health care systems by improving outcomes, ensuring patient comfort, and reducing cost.

Topics: Colectomy; Colonic Diseases; Dose-Response Relationship, Drug; Female; Gastrointestinal Agents; Humans; Ileus; Incidence; Laparoscopy; Length of Stay; Male; Michigan; Middle Aged; Piperidines; Postoperative Period; Recovery of Function; Treatment Outcome

Postoperative ileus, a temporary cessation in bowel motility, is a common and significant complication of major surgery. Consequences of postoperative ileus include increased patient discomfort, delayed time to adequate nutrition, prolonged length of stay, and increased cost to the patient and healthcare system. The traditional, multi-modal approach to the resolution of postoperative ileus includes opioid minimization, early ambulation, and early feeding. Newer medications, such as methlynaltrexone and alvimopan (which are peripherally acting mu opioid receptor antagonists), have become available and have proven beneficial for use with postoperative ileus.

Topics: Combined Modality Therapy; Exercise Therapy; Gastrointestinal Agents; Humans; Ileus; Naltrexone; Narcotic Antagonists; Piperidines; Postoperative Complications; Quaternary Ammonium Compounds

To determine whether alvimopan for prevention of postoperative ileus in patients undergoing small- or large-bowel resection by laparotomy is associated with lower total costs compared with standard care.. Pharmacoeconomic analysis using a formal decision model.. Four phase III clinical trials, two pooled analyses, and one meta-analysis.. A cohort of patients who underwent bowel resection with primary anastomosis by laparotomy and received either standardized, accelerated postoperative care (usual care) or usual care plus alvimopan.. Clinical outcomes, obtained from pooled analyses of published studies, were time to discharge order written, postoperative nasogastric tube insertion, postoperative ileus-related readmission within 7 days, and occurrence of nausea and vomiting. Cost inputs included drugs, nursing labor, readmissions, and hospitalizations. Costs were assessed by determining the net cost of alvimopan use and subsequent reduction in length of stay. Sensitivity and scenario analyses were conducted. Costs for alvimopan were $570 based on an average of 9.5 doses. Given the 18.4-hour mean reduction in time to discharge order written, use of alvimopan reduced hospitalization costs by $2021. Mean difference in overall cost of care, as determined by Monte Carlo simulation, was $1168 (95% certainty interval -$437 to $5879), favoring the use of alvimopan. In the sensitivity analysis, association of alvimopan with lower costs was robust to several changes in key parameters including cost and number of doses of alvimopan, time to discharge order written, readmission rates, and hospitalization cost. In the scenario analyses, alvimopan use yielded a net cost of $226 when no difference in time to discharge order written was assumed. In the scenario analysis using data from a study that did not enforce opioid use, alvimopan resulted in a cost saving of $65/patient.. Alvimopan was cost saving for prevention of postoperative ileus in patients undergoing bowel resection by laparotomy, although these potential cost savings were highly dependent on a difference in time to discharge order written. This finding is not applicable to the less-invasive laparoscopic surgical approach for which quality data on alvimopan use are lacking. Limitations of this analysis included use of time to discharge order written as a proxy for length of stay and difficulty interpreting study results due to inconsistent reporting and conduct of the clinical trials evaluating alvimopan. More research is needed to determine the cost-effectiveness of alvimopan.

Topics: Cohort Studies; Cost-Benefit Analysis; Decision Support Techniques; Disease Management; Economics, Pharmaceutical; Humans; Ileus; Piperidines; Postoperative Complications; Randomized Controlled Trials as Topic; Statistics as Topic

Radical cystectomy is associated with significant morbidity, with rates of gastrointestinal complications as high as 30%. Alvimopan is a mu opioid receptor antagonist that has been shown in randomized control trials to accelerate gastrointestinal recovery in patients undergoing bowel resection with primary anastamosis. We report our experience with gastrointestinal recovery for patients undergoing cystectomy with urinary diversion treated with alvimopan.. Between January 2008 and August 2011, 50 consecutive patients underwent radical cystectomy with urinary diversion at our institution. The first 27 patients in our study did not receive alvimopan preoperatively. The latter 23 patients received perioperative alvimopan and were without postoperative nasogastric decompression. Return of bowel function, initiation of diet, and gastrointestinal complications were evaluated.. Times to first flatus (3.1 versus 5.6 days, p < 0.001, 95% CI 1.66-3.26) and bowel movement (3.8 versus 6.0 days, p < 0.001, 95% CI 1.35-2.99) were significantly shorter in those patients who received alvimopan. Additionally, the initiation of clear liquid diet (4.1 versus 6.3 days, p < 0.001, 95% CI 1.20-3.12), regular diet (5.7 versus 7.3 days, p = 0.023, 95% CI 0.57-2.63) and hospital discharge (7.4 versus 9.5 days, p = 0.04, 95% CI 0.03-4.21) were accelerated in the alvimopan cohort. There were no incidences of prolonged ileus in patients who received perioperative alvimopan (0% versus 25.9%, p = 0.012).. In our experience, the use of alvimopan perioperatively significantly accelerates the rate of gastrointestinal recovery and hospital discharge, eliminates the need for nasogastric tube decompression, and reduces the incidence of postoperative ileus in patients following radical cystectomy and urinary diversion.

Topics: Aged; Analgesics, Opioid; Cystectomy; Eating; Female; Gastrointestinal Agents; Gastrointestinal Tract; Humans; Ileus; Intubation, Gastrointestinal; Length of Stay; Male; Pain, Postoperative; Piperidines; Receptors, Opioid, mu; Recovery of Function; Retrospective Studies; Time Factors; Urinary Diversion

Alvimopan, a peripherally acting μ-opioid receptor antagonist, was recently approved for the reduction of postoperative ileus after open colectomy. No data are available regarding the use of alvimopan following laparoscopic segmental colectomy.. This study was designed to evaluate the effectiveness of alvimopan in patients undergoing laparoscopic segmental colectomy.. A retrospective review of segmental laparoscopic colectomy was conducted in a population of patients using an accelerated postcolectomy care pathway. Patients that received alvimopan were identified from an institutional review board-approved database and matched with nonalvimopan patients for age, sex, procedure, and diagnosis. Patients with a diverting ileostomy or with contraindications for alvimopam were excluded.. One hundred patients undergoing laparoscopic colectomy received alvimopan perioperatively and were matched with a similar group of nonalvimopan patients. Although patients on alvimopan were significantly less likely to develop postoperative ileus (4% vs 12%; P = .04), there was no difference in length of hospital stay (3.63 days in the alvimopan group vs 3.78 in the nonalvimopan group; P = .84) or 30-day readmission rate (4.0% vs 4.2%; P = .95).. As the cost of providing health care continues to increase, reductions in perioperative complications and hospital stay are important to hospital efficiency and patient care. Alvimopan effectively reduces the incidence of postoperative ileus in patients undergoing open colectomy; however, hospital stay and readmission rates were not altered in this laparoscopic group. Further study is required before alvimopan can be routinely used in patients undergoing laparoscopic colectomy.

Topics: Analysis of Variance; Chi-Square Distribution; Colectomy; Female; Gastrointestinal Agents; Humans; Ileus; Laparoscopy; Male; Middle Aged; Piperidines; Postoperative Complications; Retrospective Studies; Treatment Outcome

Alvimopan coupled with an enhanced recovery protocol (ERP) has been shown to reduce length of stay (LOS) after open colectomy, but its role after laparoscopy remains unknown. This study evaluated alvimopan with an established ERP for laparoscopic (LAP), hand-assisted laparoscopic (HAL), and open colectomy.. Consecutive patients who underwent elective colectomy by any technique were retrospectively identified. Patients were excluded if they developed a major intra-abdominal complication, medical complication, or had a complex preoperative evaluation. Patients were stratified into 4 groups based on the surgical approach (open/HAL vs. LAP) and the use of alvimopan. All patients were managed by using an ERP. The incidence of postoperative ileus (POI) and LOS were compared between alvimopan and control groups for each surgical approach.. There were 282 patients. Demographics were similar across the 4 groups. The mean number of alvimopan doses administered was 6.7±2.6. For patients in the open/HAL group (n=149), the incidence of primary ileus was 9.5% (7/74) and 16% (12/75) for alvimopan and control patients, respectively (P=.231). A significant decrease in LOS was noted with alvimopan (5.6±2.5 vs. 6.8±3.3 days, P=.009). For patients after LAP (n=133), there was no significance difference in POI with or without alvimopan (3.9% [3/76] vs. 3.5% [2/57], P=1.00). There was no difference in LOS (3.9±1 vs. 3.7±1.4 days, P=.305).. The addition of alvimopan to an established ERP will lead to improvement in clinical outcomes in patients after open/HAL colectomy. The benefit of alvimopan after LAP remains negligible.

Topics: Clinical Protocols; Colectomy; Female; Humans; Ileus; Laparoscopy; Male; Middle Aged; Piperidines; Receptors, Opioid, mu; Retrospective Studies

Obstructive ileus is a life-threatening gastrointestinal condition that requires emergency operation. Patients with obstructive ileus sometimes develop coagulopathy. In such cases, central neuraxial blockade should be avoided. Rectus sheath blockade (RSB) is one of the popular methods for abdominal wall surgery. Ultrasound imaging of the rectus sheath may facilitate successful RSB by indicating the presence and location of rectus abdominis. Two patients presented with ileus secondary to rectal or sigmoid cancer and underwent emergency ileostomy. The patients had mild coagulopathy [platelet count, 77,000 microl(-1) in case 1, and platelet count, 98,000 microl(-1) in case 2]. Each patient underwent general anesthesia using propofol and remifentanil. They were given 0.5% ropivacaine 20ml for RSB under ultrasound-guidance. Their hemodynamics was stable and they did not need another muscle relaxant during operation, except succinylcholine during induction. RSB is useful for abdominal operations. In addition, ultrasonogrhaphy facilitates the prediction of depth of the posterior rectus sheath and improves the accuracy of local anesthetic placement. We conclude that RSB is effective for improving postoperative pain and intraoperative muscle relaxation of the abdominal wall. Ultrasound-guided RSB is an alternative method to central neuraxial blockade.

Topics: Aged, 80 and over; Anesthesia, General; Blood Coagulation Disorders; Emergencies; Female; Humans; Ileostomy; Ileus; Male; Nerve Block; Perioperative Care; Piperidines; Propofol; Rectal Neoplasms; Rectus Abdominis; Remifentanil; Sigmoid Neoplasms; Ultrasonography

BACKGROUND Cannabinoid (CB) receptors are involved in the regulation of gastrointestinal (GI) motility under physiological and pathophysiological conditions. We aimed to characterize the possible influence of CB(1) and CB(2) receptors on motility impairment in a model of septic ileus. METHODS Lipopolysaccharide (LPS) injections were used to mimic pathophysiological features of septic ileus. Spontaneous jejunal myoelectrical activity was measured in rats in vivo, and upper GI transit was measured in vivo by gavaging of a charcoal marker into the stomach of mice, in absence or presence of LPS, and CB(1) and CB(2) receptor agonists and antagonists. Tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 levels were measured using enzyme-linked immunosorbent assay. Histology was performed with haematoxylin-eosin staining. KEY RESULTS Lipopolysaccharide treatment significantly reduced amplitude and frequency of myoelectric spiking activity and GI transit in vivo in a dose-dependent manner. TNF-alpha and IL-6 were increased in LPS-treated animals and histology showed oedema and cell infiltration. Both, the CB(1) agonist HU210 and the CB(2) agonist JWH133 reduced myoelectrical activity whereas the CB(1) antagonist AM251 caused an increase of myoelectrical activity. Pretreatment with AM251 or AM630 prevented against LPS-induced reduction of myoelectrical activity, and also against the delay of GI transit during septic ileus in vivo. CONCLUSIONS & INFERENCES The LPS model of septic ileus impairs jejunal myoelectrical activity and delays GI transit in vivo. Antagonists at the CB(1) receptor or the CB(2) receptor prevent the delay of GI transit and thus may be powerful tools in the future treatment of septic ileus.

Topics: Analysis of Variance; Animals; Cannabinoids; Dose-Response Relationship, Drug; Dronabinol; Electrophysiology; Enzyme-Linked Immunosorbent Assay; Gastrointestinal Motility; Gastrointestinal Transit; Ileus; Interleukin-6; Jejunal Diseases; Jejunum; Lipopolysaccharides; Male; Piperidines; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Sepsis; Tumor Necrosis Factor-alpha

The use of anabolic steroids is a growing problem in Denmark. The effects and side effects caused by anabolic steroids in relation to anaesthesia are poorly described. This article describes a case of circulatory collapse in a young bodybuilder during anaesthesia. The primary cause of the collapse remains undetermined, but different hypotheses are proposed based on previously published literature.

Topics: Adult; Anabolic Agents; Anesthesia, Intravenous; Anesthetics, Intravenous; Humans; Ileus; Male; Neuromuscular Depolarizing Agents; Piperidines; Propofol; Remifentanil; Shock; Succinylcholine; Weight Lifting

Topics: Humans; Ileus; Piperidines; Postoperative Complications

Topics: Adult; Analgesics, Opioid; Digestive System Surgical Procedures; Drug Approval; Gastrointestinal Agents; Humans; Ileus; Piperidines; United States; United States Food and Drug Administration

Topics: Drug Discovery; Gastrointestinal Agents; Humans; Ileus; Piperidines; Postoperative Complications; Randomized Controlled Trials as Topic

Our objective was to investigate the therapeutic potential of peripheral opioid antagonism with alvimopan and anti-inflammatory cyclooxygenase 2 (COX-2) inhibition in an animal model of postoperative ileus with pain management. Intestinal manipulation was conducted in mice and rats with or without postoperative morphine injection. Rodents were orally fed non-digestible fluorescein (FITC)-labelled dextran and transit measured after a period of 90 min. The immunomodulatory effects of morphine and alvimopan were determined on nitric oxide released from the organ cultured muscularis externa. Surgical manipulation of the intestine resulted in a delay in gastrointestinal transit after 24 h that worsened with exogenous morphine. Alvimopan did not significantly alter transit of control or manipulated animals, but significantly antagonized the transit delaying effects of morphine. However, when the inflammatory component was robust enough to obscure a further opioid induced delay in gastrointestinal transit, alvimopan ceased to be effective in improving postoperative intestinal function. Cyclooxygenase 2 inhibition significantly diminished the inflammatory component of postoperative ileus. Surgical manipulation resulted in an increased release of nitric oxide from the inflamed isolated muscularis externa in 24-h organ culture which was not altered by morphine or alvimopan. Two distinct mechanisms exist which participate in postoperative bowel dysfunction: a local inflammatory response which is antagonized by COX-2 inhibition, and a morphine-induced alteration in neural function which can be blocked with alvimopan.

Topics: Analgesics, Opioid; Animals; Cyclooxygenase 2 Inhibitors; Ileus; Inflammation Mediators; Male; Mice; Mice, Inbred C57BL; Organ Culture Techniques; Piperidines; Postoperative Complications; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu

Topics: Digestive System Surgical Procedures; Gastrointestinal Agents; Humans; Ileus; Piperidines; Receptors, Opioid, mu

Postoperative ileus (PI) is a common surgical complication treated mainly with supportive measures. Tachykinins control gastrointestinal motility and modulate somatic and visceral pain sensation; therefore, the effect of tachykinin receptor antagonists in a rat model of PI using NK(1-3) antagonists, SR140333, SR48968, and SR142801, was investigated.. Intestinal transit was measured as Evans blue migration after varied nociceptive stimuli: skin incision (SI), laparotomy (LAP), or laparotomy plus gut manipulation (L + M) in anesthetized rats.. Diethyl ether anesthesia and SI did not influence the intestinal transit of the dye in comparison to untreated animals--UN: 61.17 +/- 5.47, 62.10 +/- 8.30, and 56.70 +/- 4.10 cm, respectively. In contrast LAP and L + M have significantly reduced intestinal motility to 26.40 +/- 2.07 and 9.70 +/- 1.15 cm, respectively. SR140333 (3-30 microg/kg), SR48968 (1-30 microg/kg), and SR142801 (3-10 microg/kg) reversed the additional inhibitory effects of gut manipulation subsequent to LAP dose-dependently, the dye transit returning with the use of the most effective antagonist doses up to 25.28 +/- 1.08, 21.70 +/- 0.19, and 25.0 +/- 1.34 cm. The combinations of submaximal doses of NK(1) and NK(3), NK(2) and NK(3) and NK(1), and NK(2) and NK(3) antagonists were not more effective than a single-agent regimen. On the other hand SR140333 and SR48968 (NK(1) + NK(2) antagonists) acted additively, the intestinal transit reaching 26.60 +/- 0.85 cm. SR140333, SR48968, and SR142801 have not affected the intestinal passage in UN rats or those undergoing SI or LAP.. SR140333, SR48968, and SR142801 exert a salutary action on suppressed gut motility following surgical manipulation of the gut, the combination of NK(1) and NK(2) antagonists being most beneficial.

Topics: Anesthetics, Inhalation; Animals; Antipsychotic Agents; Benzamides; Disease Models, Animal; Ether; Gastrointestinal Motility; Ileus; Male; Neurokinin-1 Receptor Antagonists; Piperidines; Postoperative Complications; Quinuclidines; Rats; Rats, Wistar; Receptors, Neurokinin-2; Receptors, Neurokinin-3; Receptors, Tachykinin

Postoperative ileus (POI) is often exacerbated by opioid analgesic use during and following surgery, since mu opioid receptor activation results in a further delay of gastrointestinal (GI) transit. The effects of alvimopan, a novel, selective, and peripherally acting mu opioid receptor antagonist, and the reference compound methylnaltrexone, upon POI were investigated in rats. Under isoflurane anesthesia, POI was induced by laparotomy with intestinal manipulation. Immediately after the surgery, the rats received (51)Cr by gavage. Three hours after the surgery, the rats were sacrificed and GI transit was estimated using the geometric center (GC) of (51)Cr. Alvimopan (0.1-3 mg/kg) or methylnaltrexone (100 mg/kg) were administered by gavage either before or after the surgery, with or without morphine administration (1 mg/kg). GI transit was delayed by intestinal manipulation (GC = 2.92 +/- 0.17). Alvimopan (1 and 3 mg/kg) significantly reversed this delayed GI transit when administered 45 min prior to surgery. However, the effects of alvimopan were less pronounced when administered following surgery. Morphine administration further delayed GI transit induced by intestinal manipulation (GC = 1.97 +/- 0.11). Under these conditions, alvimopan (1 and 3 mg/kg) also significantly improved delayed GI transit when administered before surgery. Methylnaltrexone was inactive under all experimental conditions. These data suggest that mu opioid receptors play a role in the pathogenesis of POI, and that the clinical benefit reported to be afforded by alvimopan may be in part mediated via inhibition of an endogenous opioid release as well as blockade of the unwanted GI actions of analgesic agents.

Topics: Analgesics, Opioid; Analysis of Variance; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Gastrointestinal Transit; Ileus; Laparotomy; Male; Naltrexone; Narcotic Antagonists; Piperidines; Postoperative Complications; Quaternary Ammonium Compounds; Rats; Rats, Sprague-Dawley

Topics: Abdomen; Clinical Trials as Topic; Constipation; Digestive System Surgical Procedures; Humans; Ileus; Irritable Bowel Syndrome; Narcotic Antagonists; Piperidines; Postoperative Complications; Receptors, Opioid, mu