Systemic prokinetic pharmacologic treatment for postoperative adynamic ileus following abdominal surgery in adults: Cochrane systematic review
Assessed as up to date: 2007/09/22
Postoperative adynamic bowel atony interferes with recovery following abdominal surgery. Prokinetic pharmacologic drugs are widely used to accelerate postoperative recovery.Objectives
To evaluate the benefits and harms of systemic acting prokinetic drugs to treat postoperative adynamic ileus in patients undergoing abdominal surgery.Search strategy
Trials were identified by computerised searches of the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and the Cochrane Colorectal Cancer Group specialised register. The reference lists of included trials and review articles were tracked and authors contacted.Selection criteria
Randomised controlled parallel-group trials (RCT) comparing the effect of systemically acting prokinetic drugs against placebo or no intervention.Data collection and analysis
Four reviewers independently extracted the data and assessed trial quality. Trial authors were contacted for additional information if needed.Main results
Thirty-nine RCTs met the inclusion criteria contributing a total of 4615 participants. Most trials enrolled a small number of patients and showed moderate to poor (reporting of) methodological quality, in particular regarding allocation concealment and intention-to-treat analysis. Fifteen systemic acting prokinetic drugs were investigated and ten comparisons could be summarized. Six RCTs support the effect of Alvimopan, a novel peripheral mu receptor antagonist. However, the trials do not meet reporting guidelines and the drug is still in an investigational stage. Erythromycin showed homogenous and consistent absence of effect across all included trials and outcomes. The evidence is insufficient to recommend the use of cholecystokinin-like drugs, cisapride, dopamine-antagonists, propranolol or vasopressin. Effects are either inconsistent across outcomes, or trials are too small and often of poor methodological quality. Cisapride has been withdrawn from the market due to adverse cardiac events in many countries. Intravenous lidocaine and neostigmine might show a potential effect, but more evidence on clinically relevant outcomes is needed. Heterogeneity among included trials was seen in 10 comparisons. No major adverse drug effects were evident.Authors' conclusions
Alvimopan may prove to be beneficial but proper judgement needs adherence to reporting standards. Further trials are needed on intravenous lidocaine and neostigmine. The remaining drugs can not be recommended due to lack of evidence or absence of effect.
Traut Ulrike, Brügger Lukas, Kunz Regina, Pauli-Magnus Christiane, Haug Klaus, Bucher Heiner, Koller Michael T.
Most prokinetic drugs routinely used to support bowel recovery after major abdominal surgery are not supported by current research evidence
Postoperative ileus (POI) refers to the delayed recovery of bowel function following abdominal surgery. POI may cause major patient discomfort and delayed recovery. Several drugs are commonly used to treat POI but it is unclear which drugs are supported by patient-oriented research.
Many of the 39 studies assessed in this review enrolled only a small number of patients and date back to before 1990. The novel drug alvimopan shortened bowel recovery, but many studies failed to report methodology according to current guidelines. Erythromycin, cholecystokinin, cisapride, dopamine-antagonists, propranolol or vasopressin are not supported due to lack of evidence or absence of effect. Intravenous lidocaine and neostigmine might show to be beneficial, but more evidence is needed.
Implications for practice
Pharmacological agents to decrease POI are commonly used in post-surgical management. Evidence for the majority of these agents is based on small trials of limited methodological quality compromising the interpretation of study findings. Adequately powered trials of high methodological quality are required to prove beneficial effects of any compound currently used for POI or under investigation for POI.
Limited evidence from few small trials of moderate to poor quality indicates that intravenous use of lidocaine and neostigmine may show effects on time to recovery from POI, but more evidence on patient-relevant outcomes is needed from trials with rigorous design. For cholecystokinin-like acting drugs, cisapride, dopamine-antagonists, pantothen acid, propranolol or vasopressin the evidence is insufficient to recommend their use for the treatment of POI. For all these compounds effects are either inconsistent across different outcomes, study sample sizes are too small to be conclusive, or the methodological quality of eligible trials is too poor. Cisapride has been withdrawn from the market due to adverse cardiac events in most countries worldwide. Erythromycin has no effect on GI recovery following abdominal surgery. Alvimopan may be likely to reduce time to recovery of bowel function following major abdominal surgery. However, current evidence is based on 6 trials of reasonable size but most studies do not follow current reporting standards what makes judgement of potential bias or the influence of potential conflicts of interests impossible. The compound is not yet approved for the treatment of POI.
Implications for research
Trial protocols should use an explicit rational when to start therapy for POI, should provide sufficiently long intervention and follow-up duration and use uniform endpoint reporting according to time to GI-2 and GI-3 criteria. In addition, such protocols should prohibit the use of other prokinetic drugs and use standardized protocols for pain medication with an appropriate stratified randomisation scheme for patients with epidural analgesia and laparoscopic operation techniques.
Pharmacologic treatment of POI, if proven to be effective, should furthermore be contrasted against the multimodal or proactive POI management.
Applied methodological work should elicit statistical time-to-event models most suited and clinically meaningful to report drug effects of POI data.
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