Postoperative ileus: A pharmacological perspective

Abstract

Postoperative ileus (POI) is a frequent complication after abdominal surgery. The consequences of postoperative ileus can be potentially serious such as bronchial inhalation or acute functional renal failure. Numerous advances in peri‐operative management, particularly early rehabilitation, have made it possible to decrease postoperative ileus. Despite this, the rate of prolonged postoperative ileus remains high and can be as high as 25% of patients in colorectal surgery. From a pathophysiological point of view, postoperative ileus has two phases, an early neurological phase and a later inflammatory phase, to which we could add a ‘pharmacological’ phase during which analgesic drugs, particularly opiates, play a central role. The aim of this review article is to describe the phases of the pathophysiology of postoperative ileus, to analyse the pharmacological treatments currently available through published clinical trials and finally to discuss the different research areas for potential pharmacological targets.

Post-Operative Ileus After Digestive Surgery: Network Meta-Analysis of Pharmacological Intervention.

“…Many treatments have been the subject of randomised controlled trials to decrease the rate of post-operative ileus. Nevertheless, our previous descriptive analysis of the literature did not allow us to draw clear conclusions as to the superiority of one treatment over another 5 . This finding led us to perform this network meta-analysis.…”

“…The full search strategies are listed in Supplement Table 1. They are adapted from previous systematic reviews including ones from our team's work 5 and used with bibliographic databases in combination with databasespecific filters for controlled trials where available. Trials investigating pharmacological treatments for postoperative ileus after abdominal surgery were searched by adding boundaries for randomised controlled trials (with the exploded terms "random" "trial" or "RCT").…”

“…A network approach using hierarchical Bayesian models allows indirect comparisons of pharmacological therapies for ileus after abdominal surgery and produces previously unexplored relative effectiveness. We conducted a systematic review identifying all randomised controlled trials evaluating pharmacological interventions to treat post-operative ileus after abdominal surgery 5 . After identifying the studies, we performed a networked meta-analysis of all available high-quality trials to provide new evidence in favour of pharmacological treatments to reduce ileus.…”

Molecular and cellular mechanisms underlying postoperative paralytic ileus by various immune cell types

“…Current approaches to prevent or treat ileus include non-pharmacological interventions and pharmacological treatments ( Wattchow et al, 2021 ), most of which have poor therapeutic effects and lacks reliable clinical evidence ( Delaney et al, 2010 ; Sammut et al, 2021 ). Hence, new strategies that target the intimate mechanisms of POI are required to complement current clinical practice and solve existing medical dilemmas ( Buscail and Deraison, 2022 ). Recent studies have focused on the intestinal inflammation during POI, and as key components of inflammatory response, the populations of immune cells including monocytes, macrophages, neutrophils, dendritic cells, mast cells, and T lymphocytes, are proved to be closely linked to the onset of POI.…”

“…In the initial phase, such interactions can be influenced by active substances secreted from MCs, which causes neurogenic inflammation and increased sensitivity. These effects on neurons eventually promote the disturbances of gut motility ( Buscail and Deraison, 2022 ). Previous experiments on mouse models showed that gut manipulation led to mast cell degranulation and this process contributed to the development of leukocyte infiltration, implicating that MCs played a key role in the inflammatory cascade during POI ( De Jonge et al, 2004 ).…”