The management of postoperative ileus

Postoperative ileus remains a serious clinical problem. It is 1 of the most important contributors to increased length of hospitalization and consumption of the health care system resources. Shortening the mean length of stay by as little as 1 day may reduce the annual health care system costs by approximately US $1 billion.²⁴⁸ In view of this tremendous medical and economical burden, a search for efficient ways to “cure” postoperative ileus has been ongoing for decades, with substantial progress in the last few years.The etiology of postoperative ileus includes several individual mechanisms that interact during the postoperative period. Currently, it is widely accepted that the combined effects of inhibitory sympathetic input, inflammation, and opioid analgesics lead to significant impairment of bowel motility in the postoperative period. Due to this multifactorial etiology, attempts have been made to address each proposed cause individually, and also to treat several causes simultaneously to quickly restore normal postoperative bowel motility, or prevent it from malfunctioning altogether.Minimally invasive surgical techniques induce less mechanical trauma and postoperative pain. Consequently, the sympathetic, metabolic, and inflammatory responses are attenuated, and the need for aggressive pain control is reduced. The result is faster restoration of normal body functions including GI function. Although currently laparoscopy still is not indicated for every procedure, the indications are constantly expanding. Specifically in colorectal surgery and in GI surgery in general, nearly every procedure has already been performed laparoscopically with favorable outcomes.The medical control of postoperative pain has experienced significant advances as well. Opiates have been the mainstay of postoperative pain control for decades. Their deleterious effects, including the effects on the GI tract, have been accepted as an inevitable consequence of an otherwise indispensable medication. The understanding of the mechanisms that lead to postoperative ileus introduced epidural blockade with local anesthetics as an attractive alternative to opiates. The technical difficulties were overcome quickly, and the technique gained increasing popularity despite some controversies with regard to efficacy and outcome. The introduction of alternative analgesics was another advancement. Nonsteroidal anti-inflammatory agents have been shown to be extremely efficient analgesics on top of their anti-inflammatory characteristics. The new, selective COX-2 inhibitors have an additional advantage of having fewer adverse effects.Intuitively, investigators presumed that combining the beneficial effects of several treatment modalities would result in a combined, synergistic effect. This idea introduced the multimodal approach to postoperative management of the surgical patient. The basic protocol includes minimally invasive surgery, followed by aggressive, opiate-free pain control, avoidance of NGTs that have been consistently shown to prolong ileus and length of stay, and early oral feeding and ambulation. The latter 2 modalities do not reduce the duration of postoperative ileus, but they can reduce the incidence of other postoperative complications, thereby shortening the length of hospitalization.The multimodal approach, or fast-track surgery, demonstrated very encouraging results and is now the standard of care in many facilities around the world. The shorter length of stay is attributed to several factors, including the reduction of the duration of postoperative ileus. Although a cure for postoperative ileus has not yet been invented, significant progress toward that goal indeed has been accomplished.     

Prevention of postoperative ileus

Postoperative ileus (PI) is a major contributor to postoperative morbidity and prolonged convalescence after major surgical procedures. The pathophysiology of PI is multifactorial, including activation of the stress response to surgery, with inhibitory sympathetic visceral reflexes and inflammatory mediators. We update evidence on the advances in the prevention and treatment on PI. As single interventions, continuous thoracic epidural analgesia with local anesthetics and minimally invasive surgery are the most efficient interventions in the reduction of PI. The effects of pharmacological agents have generally been disappointing with the exception of cisapride and the introduction of the new selective peripherally acting m-opioid antagonists. Presently, introduction of a multi-modal rehabilitation programme (including continuous epidural analgesia with local anesthetics, early oral feeding and enforced mobilization) is the most effective technique to reduce PI in abdominal procedures.     

Management of postoperative ileus

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.     

Immune mediators of postoperative ileus

Clinical background  

In all patients undergoing abdominal surgery, a transient phase of interruption of bowel motility, named postoperative ileus (POI) occurs. POI is often accepted as an unavoidable “physiological” response and a self-limiting complication after surgery although it has a significant impact on patient morbidity with prolonged hospitalization and increased costs. Annual economic burden has been estimated as much as US $1.47 billion in the USA (Iyer et al. in J Manag Care Pharm 15(6):485–494, 2009).     

小肠内支撑排列术治疗多次术后广泛粘连性肠梗阻

目的总结小肠内支撑排列术治疗多次术后广泛粘连性肠梗阻的临床经验与疗效。方法回顾分析1995～2003年间采用小肠内支撑排列术治疗多次术后广泛粘连性肠梗阻21例患者的临床资料。结果20例患者术后无并发症发生,顺利康复。1例肠坏死肠切除病例术后发生肠瘘,经内支撑管持续低负压引流后迅速痊愈。19例患者经1～7年随访,均未出现肠粘连和肠梗阻。结论对多次手术(2次以上)后出现广泛粘连性肠梗阻患者,小肠内支撑排列术是一种操作简单、安全而有效的术式。     

Mechanisms and treatment of postoperative ileus

OBJECTIVE: To review the pathogenesis and treatment of postoperative ileus. DATA SOURCES: Data collected for this review were identified from a MEDLINE database search of the English-language literature. The exact indexing terms were "postoperative ileus," "treatment," "etiology," and "pathophysiology." Previous review articles and pertinent references from those articles were also used. STUDY SELECTION: All relevant studies were included. Only articles that were case presentations or that mentioned postoperative ileus in passing were excluded. DATA SYNTHESIS: The pathogenesis of postoperative ileus is complex, with multiple factors contributing either simultaneously or at various times during the development of this entity. These factors include inhibitory effects of sympathetic input; release of hormones, neurotransmitters, and other mediators; an inflammatory reaction; and the effects of anesthetics and analgesics. Numerous treatments have been used to alleviate postoperative ileus without much success. CONCLUSIONS: The etiology of postoperative ileus can best be described as multifactorial. A multimodality treatment approach should include limiting the administration of agents known to contribute to postoperative ileus (narcotics), using thoracic epidurals with local anesthetics when possible, and selectively applying nasogastric decompression.     

Pharmacological management to prevent ileus in major abdominal surgery: a systematic review and meta-analysis

Background

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.

Objective

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 sources

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.

Study selection

Only randomized trials were eligible for inclusion.

Interventions

Opioid receptor antagonists, ghrelin receptor agonists and serotonin receptor agonists used for the prevention of postoperative ileus in gastrointestinal surgery.

Main outcome measures

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.

Results

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.

Limitations

Most of the trials were poorly reported and of mixed quality. Future studies must focus on the development of a set of core outcomes.

Conclusions

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.

     

Effects of propranolol on human postoperative ileus

BACKGROUND: The sympathetic nervous hyperactivity present in response to surgical stress has been implicated as an important component of the postoperative paralytic ileus. A randomized and prospective study was conducted, evaluating the effects of the preoperative beta-adrenergic blockade with propranolol in schistosomotic patients during the period of postoperative ileus. METHODS: The study compared schistosomotic patients submitted, or not, to beta-adrenergic blockade. Basal cardiac frequency was determined and propranolol was used in a dose of 40 mg twice a day. The dose was adjusted weekly until a minimum decrease of 20% in cardiac frequency was achieved. Three coupled bipolar electrodes were placed in the left colon in both groups, and registration of myoelectric activity of the left colon was made twice a day during the period of postoperative ileus using a system of data collection (DATA Q Series 200). The electric signals were previously amplified, filtered and separated into Electric Control Activity (ECA) and Electric Response Activity (ERA). RESULTS: The dose of propranolol varied from 80 to 160 mg/day. The proportional decrease in basal heart frequency varied from 20 to 33%, with an average of 25.4 +/- 3.9% in the propranolol group, maintaining a mean of 24.3 +/- 3.6% decrease in the postoperative period. Differences on clinical recovery of the postoperative ileus were not found. Significant differences on electromyographic patterns were not observed between the groups, except for the presence of a greater number of short-duration contractions in the second postoperative day in the beta-blocked group. CONCLUSION: The authors suggest that the preoperative beta-adrenergic blockade with propranolol does not determine myoelectric activity changes that could contribute to an earlier resolution of postoperative ileus.     

术后肠麻痹发病机制的研究进展

术后肠麻痹通常指腹部手术后引起的胃肠运动功能的抑制.影响手术患者胃肠运动功能的因素是多方面的,如疼痛、手术操作和电解质平衡紊乱等.虽然多数患者症状较轻,胃肠运动功能常于术后短期内自行好转,但仍有少数患者胃肠运动紊乱的时间持续较长,治疗困难,由此加重病情,延长术后康复,延长住院时间以及增多治疗费用等.明确术后肠麻痹的病因和发病机制有助于对其进行防范和治疗.     

Resolution of postoperative ileus in humans.

Bipolar electrodes were placed in the ascending and descending colon of 13 patients during laparotomy. The magnitude of their operations varied from exploratory laparotomy to total gastrectomy. The magnitude and length of the operations performed did not correlate positively with the duration of postoperative ileus. Signals were recorded for up to 4 hours daily for up to 8 days after operation during periods of rest and, in some patients, after administration of epidural or parenteral morphine sulfate. Power spectrum analyses of electrical control activity (ECA) showed dominant frequencies in both lower (2-9 cpm) and higher (9-14 cpm) ranges. During postoperative recovery, the mean ECA frequencies in right and left colon were relatively constant, but a variety of dominant ECA frequency relationships were observed. The modal pattern in the right colon was a shift in the dominant frequency from the higher to the lower range as recovery progressed, while the modal pattern in the left colon was persistent dominance of ECA in the higher frequency range. Electrical response activity (ERA) initially was comprised of only random, disorganized single bursts but became progressively more complex through the initial 3 postoperative days with the appearance of more organized bursts and clusters, some of which propagated very slowly (about 5 cm/min) both orad and aborad. ERA recovery culminated, typically on the third or fourth postoperative day, with the return of long bursts of continuous ERA, some of which propagated at a higher velocity (about 80 cm/min) and exclusively in the aborad direction and which were accompanied by passage of flatus or by defecation.     

Prevention and therapy of postoperative paralytic ileus

An analysis of the course of the postoperative period has shown that continuous mesenterial retroperitoneal novokain blockade is considerably more effective than medicamentous methods of prophylactics and treatment of postoperative paresis of the intestine, it has a good anesthetizing effect. When using the blockade the intestine function was completely reestablished in 111 (92.5%) patients operated upon.     

Placebo-controlled trial of cisapride in postoperative ileus

The effect of 4 mg of the gastrointestinal motility enhancing agent cisapride on postoperative ileus was compared with that of a placebo in 53 patients who had undergone various types of surgery. They received one i.v. injection of the double-blind medication, or two if no distinct flatus occurred within an hour after the first injection. The placebo response was very limited; borborygmi or flatus did not occur in more than 12% of the patients not even after the second injection. Cisapride was significantly effective: bowel sounds were present in 43% and 50% within 1 hour after the first and second injection of 4 mg, respectively, and flatus in 36% and 43%. The recognition that colon inactivity probably is the major determinant of the ileus, may be indicative of a substantial relative impact of cisapride's stimulating effects on colon motility.