In patients who have their bladder removed, does the drug alvimopan compared to placebo help them recover their bowel function more quickly?
Surgical removal of the bladder is a major operation that requires a stay of several days in hospital. One of the issues that keeps patients in hospital is not being able to eat normal food and not having bowel movements, an issue that is referred to as ileus. Alvimopan is a drug that is being used to treat this problem but it is uncertain how well it works and what its side effects are when used in this setting.
We performed a comprehensive literature search for randomized controlled trials and found one study that addressed our question. This study was a randomized trial of adults undergoing surgery to remove their bladder. They received either 12 mg alvimopan of up to 15 doses over seven days (143 patients) or placebo (137 patients). This study was conducted at centres that did many of these operations (at least 50 per year), had experienced surgeons and also used other measures such as asking patients to get out of bed soon after surgery to hasten bowel recovery.
We found that patients who receive alvimopan short-term probably tolerate solid food faster, are discharged from the hospital more quickly and have fewer major adverse events. We did not find any differences with regards to these patients' need to be readmitted to hospital, their risk of heart problems or their need for narcotic pain medications. Patients taking alvimopan were less likely to have a tube placed back into their stomach.
Quality of the evidence
The quality of evidence was rated as at least moderate as per GRADE for all primary outcomes. This means that our estimates of how well alvimopan works is likely close to how well it really works although there is a possibility that it may be different.
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.
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.