Background: Postoperative ileus (POI) is one of the most common postoperative complications after colorectal surgery and prolongs hospital stays. Minimally invasive surgery (MIS) has reduced POI, but it remains common. This review explores the current methods for preventing and managing POI after MIS. Summary: Preoperative interventions, including optimising nutrition, preoperative medicationn, and mechanical bowel preparation with oral antibiotics, may have a role in preventing POI. Transversus abdominis plane blocks and lidocaine could replace epidural analgesia in MIS. Fluid overload should be avoided; in some cases, goal-directed fluid therapy may aid in achieving this. Pharmacological agents, such as prucalopride and dexmedetomidine, could target mechanisms underlying POI. New strategies to stimulate vagal nerve activity may promote postoperative gastrointestinal motility. Preoperative bowel stimulation could potentially reduce POI following loop ileostomy closure. However, the evidence base for several interventions remains weak and requires further corroboration with robust studies. Key Messages: Despite the increasing use of MIS, POI remains a major issue following colorectal surgery. Further strategies to prevent POI are rapidly emerging. Studies using standardised definitions and perioperative care will help validate these interventions and remove barriers to accurate meta-analysis. Future studies should focus on establishing the impact of these interventions on POI after MIS specifically.

Postoperative ileus (POI) is a very common postoperative complication and is estimated to affect 10–30% of patients after colorectal surgery [1]. POI is known to increase hospital stays, postoperative complications, and readmission rates, making it a significant financial and resource burden [2]. It was hoped that minimally invasive surgery (MIS) would markedly reduce POI as it involves less bowel manipulation, smaller incisions, and reduced tissue trauma [3]. This decreases inflammatory response to surgery which is a key in the pathophysiology of POI. However, database analysis found that 10% of patients undergoing laparoscopic colectomy still develop prolonged POI and therefore further strategies to prevent POI will benefit many individuals as well as wider healthcare systems [4]. There is a gap in the literature on a single article that summarises the currently available knowledge on POI after MIS and ongoing strategies to reduce its rate which this article will address.

Definitions

An initial period of POI is typically a self-limiting response to colorectal surgery and is sometimes referred to as physiological or obligatory POI [5]. When POI symptoms are experienced for a more sustained duration, this is referred to as prolonged POI (PPOI). Experiencing symptoms of POI for >4 days is considered the threshold PPOI as determined by a global survey [2].

Differing definitions of POI result in significant variations in reported incidence even within the same population [1]. It has been suggested that PPOI should be diagnosed when at least two of the following are present on or after the 4th postoperative day: nausea and vomiting, an inability to tolerate solid or semi-liquid diet during the preceding 24 h, no gas or stool for the preceding 24 h, abdominal distension, or radiological evidence of ileus [2]. This definition is now in wider use, but significant variation still exists in the definitions of POI used across the literature.

Diagnosis

Diagnosis of POI is mostly based on clinical criteria rather than radiological or physiological measures. Several studies use a composite outcome of time taken to both pass stool and tolerate solid food, sometimes referred to as “GI-2 outcome.” This combined outcome is validated against scintigraphy measurements of postoperative gastrointestinal motility and is considered the best reflection of colonic transit recovery after surgery [6]. Furthermore, it revealed that the time to first flatus and bowel sounds were not good indicators of colonic transit.

Several studies attempted to determine the risk factors for POI after colorectal surgery; however, there is significant variation across studies. This inconsistency is due to differing definitions of POI, heterogeneity between studies, and the retrospective methods used in many studies. Factors identified to increase POI include male sex, low preoperative albumin, open/converted surgery, increasing wound size, operative difficulty, red cell transfusions, intravenous crystalloid administration, and delayed mobilisation [3].

Pathophysiology

The pathophysiology of POI is not fully understood but is thought to involve an early neural-mediated phase followed by a later inflammatory phase [7]. In the initial neurological phase, noxious surgical stimuli activate splanchnic and vagal pathways which disturb gastrointestinal motility [5]. Once surgery concludes, surgical stimuli no longer activate these pathways; however, inflammatory mediators continue to activate them which accounts for the sustained nature of PPOI. The inflammatory phase is considered a significant contributor to PPOI so is often the target for interventions to prevent or resolve POI [5].

This inflammatory phase begins 3–4 h after surgery and is related to the degree of bowel handling. Bowel manipulation stimulates inflammatory cells, resulting in inflammatory infiltration of the bowel wall and increased intestinal permeability with bowel wall oedema [5]. Additionally, bowel handling activates macrophages in the muscularis externa which release mediators, such as nitric oxide, which impair smooth muscle contraction and decrease bowel motility [8, 9]. Less bowel manipulation is likely responsible for the reduction in POI rates seen after MIS compared to open surgery.

The cholinergic anti-inflammatory pathway is essential in the resolution of POI [5]. Stimulation of enteric neurones results in the release of acetylcholine, which acts on α7nACh receptors present on monocytes and macrophages to reduce the inflammatory response [8]. Activation of this pathway, pharmacologically or electrically, forms the basis for several strategies to prevent POI.

It should be noted that most studies for POI pathophysiology are based on murine models of POI induced by small intestine manipulation, so this should be considered carefully when extrapolating results into clinical practice. Recently, a high-resolution manometry study in humans undergoing colorectal surgery challenged the assumption that the gastrointestinal tract is inhibited following surgery and instead found that motility in the distal colon becomes hyperactive postoperatively, which could act as a functional obstruction contributing to postoperative bowel dysfunction [10]. Further research must establish the exact dysmotility patterns experienced in humans following colorectal surgery.

The following databases were searched from January 1995 to December 2022: OVID/Embase, Scopus, PubMed/Medline, Cochrane library, Google Scholar, Web of Science, and ProQuest. Databases were searched using these search terms: ([post-operative ileus OR post-surgical ileus OR post-op ileus OR post-operative paresis OR POI OR PPOI OR post-operative atony OR paralytic ileus OR a dynamic ileus] AND [laparoscopic surgery OR MIS OR keyhole surgery OR laparoscopy] AND [colon OR rectal OR rectum OR large bowel OR large intestine OR colorectal]). Only sources available in English with full text access were included. Deduplication of papers was performed by Mendeley. The remaining literature was screened to determine their relevance to the review question. Reference lists were searched manually. The main articles are summarised in Table 1. Strategies for prevention and management of POI were summarised as a narrative review.

Table 1.

Summary of the main studies on the incidence of POI included in the review

Study (first author and date of publication)Study typePatients, nSurgical approach (open/MIS/both)Measure to prevent POIIncidence of POI in study groups, %Additional comments, if any
Laparoscopic surgery within an enhanced after surgery (ERAS) protocol reduced postoperative ileus by increasing postoperative treg levels in patients with right-sided colon carcinoma. Wang H et al. [11] (2018) Prospective 176 Both (open n = 90, MIS n = 86) MIS Overall ileus in open surgery: 41.1 Early ileus defined as “presence of 1 or more of the following symptoms: >1 episode of vomiting or nausea, or reinsertion of the nasogastric tube in the first 5 days; the use of a nasogastric tube for more than 4 days; and no recover of euphagia after 5 days or no first-time normal defecation within 7 days“ 
Overall ileus in MIS: 25.6 Late ileus defined as “Vomiting or nausea during the first 5 days that necessitated reinsertion of the nasogastric tube or that influenced defecation and normal intake” 
Early ileus in open surgery: 22.2 Prolonged ileus was defined as early ileus lasting more than 5 days 
Early ileus in MIS: 9.3 When evaluating prolonged POI specifically there was only a reduction from 10% to 8.1% which was not statistically significant 
Late ileus in open surgery: 8.9 
Late ileus in MIS: 8.1 
Prolonged ileus in open surgery: 10 
Prolonged ileus in MIS: 8.1 
The impact of operative approach on postoperative outcomes and healthcare utilization after colectomy. Mlambo B et al. [12] (2022) Retrospective 206,967 Both Robotic surgery Open left colectomy: 13.4 Definition of POI not stated 
Laparoscopic left colectomy: 9.6 
Robotic left colectomy: 7 
Open right colectomy: 15.4 
Laparoscopic right colectomy: 12.4 
Robotic right colectomy: 9.8 
Does enhanced recovery reduce postoperative ileus after colorectal surgery? Barbieux J et al. [1] (2017) Prospective 131 Both ERAS protocol PPOI in groups with <85% adherence to ERAS protocol: 46.5 POI was defined as at least two of the following: nausea or vomiting for 12 hours, inability to tolerate a solid or semi-solid food for two meals, abdominal distension, lack of stool or gas for 24 hours, radiologic images of ileus on computed tomography scan 
PPOI in groups with >85% adherence to ERAS protocol: 26.75 PPOI was defined as POI lasting ≥4 days 
Combination of oral and mechanical bowel preparations decreases complications in both right and left colectomy. Midura EF et al. [13] (2018) Retrospective 45,724 Both MBP + oral antibiotics No preparation: 12.7 Definition of POI not stated 
MBP only: 11.4 
Antibiotics only: 11.3 
MBP + antibiotics: 9.2 
Insufficient postoperative energy intake is associated with failure of enhanced recovery programs after laparoscopic colorectal cancer surgery: a prospective cohort study. Liu S et al. [14] (2021) Prospective 91 MIS ERAS All patients: 28.6 Definition of POI not stated 
ERAS failure: 53.8 
ERAS success: 23.1 
Usefulness of gum chewing to decrease postoperative ileus in colorectal surgery with primary anastomosis: a randomized controlled trial. Vergara-Fernandez O et al. [15] (2016) RCT 64 Both Chewing gum Standard postoperative recovery group: 22 POI was defined as “absence of adequate bowel function on postoperative day 5 or the need for the insertion of a nasogastric tube because of abdominal distension, nausea, and emesis after having started a liquid diet, in the absence of mechanical obstruction” 
Chewing gum group: 6 
Decreased opioid consumption and enhance recovery with the addition of IV acetaminophen in colorectal patients: a prospective, multi-institutional, randomized, double-blinded, placebo-controlled study (DOCIVA study). Aryaie AH et al. [16] (2018) RCT 97 Both IV acetaminophen Control: 22 POI defined as nausea and vomiting with abdominal X-ray findings consistent with ileus 
Acetaminophen: 2.1 
Preoperative intravenous meloxicam for moderate-to-severe pain in the immediate postoperative period: a phase IIIb randomized clinical trial in 55 patients undergoing primary open or laparoscopic colorectal surgery with bowel resection and/or anastomosis. Silinsky JD et al. [17] (2020) RCT 55 Both IV meloxicam 30 min prior to surgery Control: 17.9 Definition of POI not stated 
Meloxicam: 3.7 
Alvimopan addition to a standard perioperative recovery pathway. Itawi EA et al. [18] (2011) Retrospective 165 MIS Alvimopan Control: 20 POI diagnosis was made by the surgeon at the time of the hospital stay and was recorded in the discharge summary. A patient was classified as having experienced POI only if the diagnosis of POI was present in the discharge summary 
Alvimopan: 2 
Is there value in alvimopan in minimally invasive colorectal surgery? Keller DS et al. [19] (2016) Case-matched analysis 622 MIS Alvimopan Control: 2.2 Definition of POI not stated 
Alvimopan: 2.2 
Stimulation of the efferent limb before ileostomy closure: a randomized clinical trial. Abrisqueta J et al. [20] (2014) RCT 70 Both Stimulation of efferent ileostomy limb with thickening agent No preoperative stimulation: 20 POI was defined as “intolerance to oral food in the absence of clinical and radiological data of mechanical obstruction (abdominal pain, muscular guarding, and slight dilation of the small bowel) for more than 72 hours, or the need for a nasogastric tube” 
Stimulation: 2.85 
Bowel stimulation before loop ileostomy closure to reduce postoperative ileus: a multicenter, single-blinded, randomized controlled trial. Garfinkle R et al. [21] (2022) RCT 96 Both (open n = 35, MIS n = 61) Stimulation of efferent ileostomy limb with thickening agent No preoperative stimulation: 24.5 POI defined as “an intolerance to oral food in the absence of clinical or radiological signs of obstruction on or after postoperative day 3 that either (a) required nasogastric tube insertion or (b) was associated with two of the following: nausea/vomiting, abdominal distension, or the absence of flatus” 
Stimulation: 6.4 
Study (first author and date of publication)Study typePatients, nSurgical approach (open/MIS/both)Measure to prevent POIIncidence of POI in study groups, %Additional comments, if any
Laparoscopic surgery within an enhanced after surgery (ERAS) protocol reduced postoperative ileus by increasing postoperative treg levels in patients with right-sided colon carcinoma. Wang H et al. [11] (2018) Prospective 176 Both (open n = 90, MIS n = 86) MIS Overall ileus in open surgery: 41.1 Early ileus defined as “presence of 1 or more of the following symptoms: >1 episode of vomiting or nausea, or reinsertion of the nasogastric tube in the first 5 days; the use of a nasogastric tube for more than 4 days; and no recover of euphagia after 5 days or no first-time normal defecation within 7 days“ 
Overall ileus in MIS: 25.6 Late ileus defined as “Vomiting or nausea during the first 5 days that necessitated reinsertion of the nasogastric tube or that influenced defecation and normal intake” 
Early ileus in open surgery: 22.2 Prolonged ileus was defined as early ileus lasting more than 5 days 
Early ileus in MIS: 9.3 When evaluating prolonged POI specifically there was only a reduction from 10% to 8.1% which was not statistically significant 
Late ileus in open surgery: 8.9 
Late ileus in MIS: 8.1 
Prolonged ileus in open surgery: 10 
Prolonged ileus in MIS: 8.1 
The impact of operative approach on postoperative outcomes and healthcare utilization after colectomy. Mlambo B et al. [12] (2022) Retrospective 206,967 Both Robotic surgery Open left colectomy: 13.4 Definition of POI not stated 
Laparoscopic left colectomy: 9.6 
Robotic left colectomy: 7 
Open right colectomy: 15.4 
Laparoscopic right colectomy: 12.4 
Robotic right colectomy: 9.8 
Does enhanced recovery reduce postoperative ileus after colorectal surgery? Barbieux J et al. [1] (2017) Prospective 131 Both ERAS protocol PPOI in groups with <85% adherence to ERAS protocol: 46.5 POI was defined as at least two of the following: nausea or vomiting for 12 hours, inability to tolerate a solid or semi-solid food for two meals, abdominal distension, lack of stool or gas for 24 hours, radiologic images of ileus on computed tomography scan 
PPOI in groups with >85% adherence to ERAS protocol: 26.75 PPOI was defined as POI lasting ≥4 days 
Combination of oral and mechanical bowel preparations decreases complications in both right and left colectomy. Midura EF et al. [13] (2018) Retrospective 45,724 Both MBP + oral antibiotics No preparation: 12.7 Definition of POI not stated 
MBP only: 11.4 
Antibiotics only: 11.3 
MBP + antibiotics: 9.2 
Insufficient postoperative energy intake is associated with failure of enhanced recovery programs after laparoscopic colorectal cancer surgery: a prospective cohort study. Liu S et al. [14] (2021) Prospective 91 MIS ERAS All patients: 28.6 Definition of POI not stated 
ERAS failure: 53.8 
ERAS success: 23.1 
Usefulness of gum chewing to decrease postoperative ileus in colorectal surgery with primary anastomosis: a randomized controlled trial. Vergara-Fernandez O et al. [15] (2016) RCT 64 Both Chewing gum Standard postoperative recovery group: 22 POI was defined as “absence of adequate bowel function on postoperative day 5 or the need for the insertion of a nasogastric tube because of abdominal distension, nausea, and emesis after having started a liquid diet, in the absence of mechanical obstruction” 
Chewing gum group: 6 
Decreased opioid consumption and enhance recovery with the addition of IV acetaminophen in colorectal patients: a prospective, multi-institutional, randomized, double-blinded, placebo-controlled study (DOCIVA study). Aryaie AH et al. [16] (2018) RCT 97 Both IV acetaminophen Control: 22 POI defined as nausea and vomiting with abdominal X-ray findings consistent with ileus 
Acetaminophen: 2.1 
Preoperative intravenous meloxicam for moderate-to-severe pain in the immediate postoperative period: a phase IIIb randomized clinical trial in 55 patients undergoing primary open or laparoscopic colorectal surgery with bowel resection and/or anastomosis. Silinsky JD et al. [17] (2020) RCT 55 Both IV meloxicam 30 min prior to surgery Control: 17.9 Definition of POI not stated 
Meloxicam: 3.7 
Alvimopan addition to a standard perioperative recovery pathway. Itawi EA et al. [18] (2011) Retrospective 165 MIS Alvimopan Control: 20 POI diagnosis was made by the surgeon at the time of the hospital stay and was recorded in the discharge summary. A patient was classified as having experienced POI only if the diagnosis of POI was present in the discharge summary 
Alvimopan: 2 
Is there value in alvimopan in minimally invasive colorectal surgery? Keller DS et al. [19] (2016) Case-matched analysis 622 MIS Alvimopan Control: 2.2 Definition of POI not stated 
Alvimopan: 2.2 
Stimulation of the efferent limb before ileostomy closure: a randomized clinical trial. Abrisqueta J et al. [20] (2014) RCT 70 Both Stimulation of efferent ileostomy limb with thickening agent No preoperative stimulation: 20 POI was defined as “intolerance to oral food in the absence of clinical and radiological data of mechanical obstruction (abdominal pain, muscular guarding, and slight dilation of the small bowel) for more than 72 hours, or the need for a nasogastric tube” 
Stimulation: 2.85 
Bowel stimulation before loop ileostomy closure to reduce postoperative ileus: a multicenter, single-blinded, randomized controlled trial. Garfinkle R et al. [21] (2022) RCT 96 Both (open n = 35, MIS n = 61) Stimulation of efferent ileostomy limb with thickening agent No preoperative stimulation: 24.5 POI defined as “an intolerance to oral food in the absence of clinical or radiological signs of obstruction on or after postoperative day 3 that either (a) required nasogastric tube insertion or (b) was associated with two of the following: nausea/vomiting, abdominal distension, or the absence of flatus” 
Stimulation: 6.4 

Minimally Invasive Surgery

Laparoscopic colorectal surgery can significantly reduce the rates of POI compared to open surgery [22]. Furthermore, laparoscopic colon resection reduced increases in postoperative C-reactive protein levels, restored circulating CD4+/CD8+ T cell ratio quicker, and increased expression of Treg compared to open resection. This resulted in reduction in overall incidence of POI from 41.1 to 25.6% [11]. However, a meta-analysis did not identify any differences in POI rates between MIS and open approaches [23]. This may be due to variations in POI definitions and endpoints.

Robotic colorectal surgery is associated with reductions in POI rates compared to both open and laparoscopic surgery. It also significantly decreased the rates of conversion to open surgery [12]. More studies are needed to determine its influence on development of POI compared to laparoscopic surgery.

Implementation of Enhanced Recovery after Surgery Protocols

Compliance with ≥85% of enhanced recovery after surgery (ERAS) measures is associated with a significant reduction in prolonged POI after colectomies from 46.5 to 26.75% [1]. It has been suggested that the emergence of ERAS protocols has improved postoperative outcomes regardless of surgical approach, making MIS less advantageous. However, MIS in combination with ERAS protocols has been identified as superior in improving colonic transit, shown by scintigraphy and shortening time to GI-2 outcome compared to open colorectal surgery [24]. The effect of ERAS protocols is difficult to establish due to a lack of standardisation across institutions. Additionally, their multimodal nature complicates identifying which interventions are responsible for benefits. With the emergence of MIS, individual components of ERAS protocols should be evaluated for their benefits with regards to MIS specifically.

Mechanical and Oral Antibiotic Bowel Preparation

Previous ERAS guidelines recommended avoiding mechanical bowel preparation (MBP) before colon surgery because it was associated with dehydration and POI and did not show benefits compared with no bowel preparation [25]. More recently, the combination of oral antibiotics and MBP has been investigated. In a retrospective database review of over 45,000 cases, MBP with oral antibiotics before open and laparoscopic colorectal surgery decreased POI rates compared to no bowel preparation and MBP alone (9.2 vs. 12.7 vs. 11.4%) [13]. The addition of preoperative oral antibiotics to intravenous antibiotics and MBP significantly reduced POI rates after colorectal surgery in three cohort studies but not in two RCTs [26]. The most recent ERAS guidelines maintain that MBP alone has no clinical benefit and should be avoided but recognises that there is some evidence supporting MBP with oral antibiotics [27]. The role of MBP with preoperative oral antibiotics with regards to MIS specifically needs to be further investigated with future RCTs.

Perioperative Fluid Management

There is debate about optimal intraoperative fluid management. Perioperative fluid administration resulting in weight gain >2·5 kg on postoperative day 2 is independently associated with POI after laparoscopic colorectal surgery [28]. Goal-directed fluid therapy (GDFT) uses objective clinical indicators to guide intraoperative fluid administration to optimise a patient’s haemodynamic state [29]. However, a meta-analysis comparing GDFT and conventional fluid therapy in open and laparoscopic colorectal surgery found no significant differences in POI incidence or gastrointestinal recovery. Subgroup analysis showed that time to flatus and tolerating oral diet were significantly shorter in patients receiving GDFT without an ERAS protocol, so GDFT may be of more benefit in these patients [29]. Future studies focussing on intraoperative fluid management in MIS specifically are needed.

Postoperative fluid management also needs careful consideration. Once oral fluid intake is established, intravenous fluid infusion should be stopped and should not be restarted unless clinically indicated [27]. An association between serum electrolyte imbalances and PPOI after colorectal surgery has been identified, especially sodium and chloride imbalances. It is yet to be established if these are contributing to POI or a result of it, but postoperative electrolyte derangements should be corrected since their effects on cellular electrophysiology may contribute to the duration and severity of POI [30].

Nutrition

ERAS protocols discourage preoperative fasting and encourage early postoperative oral intake [27]. An association between low preoperative albumin levels and POI after open and laparoscopic colorectal surgery has been identified [3]. Low preoperative albumin may indicate poor nutritional status; therefore, interventions to improve preoperative nutrition and albumin levels may reduce POI. A prospective study reported that insufficient postoperative energy intake was associated with the failure of ERAS programmes after laparoscopic colorectal surgery. POI incidence with the failure of the ERAS programme was 53.8% compared to 23.1% when the programme was successful [14]. Early postoperative feeding could prevent insufficient energy intake and improve these outcomes. Another study demonstrated that compliance with early postoperative nutrition decreased the risk of POI after both laparoscopic and open colorectal surgery [31]. Overall, early postoperative feeding should be encouraged as it may stimulate bowel function recovery.

Coffee Consumption

Significantly shorter time to defecation was found in patients drinking coffee after open or laparoscopic colectomy compared to water [32]. Consuming coffee after laparoscopic left-sided colectomy shortened the time to defecation compared to water, but interestingly decaffeinated coffee significantly shortened time to defecation compared to caffeinated coffee and water (3.00 ± 1.50 vs. 3.75 ± 1.53 vs. 4.14 ± 1.14 days) [33]. Additionally, time to tolerate solid food was significantly shorter (1.85 vs. 2.60 and 2.80 days). This indicates that caffeine is not the only coffee ingredient that stimulates bowel motility. Future studies should evaluate the effects of other coffee components on POI incidence.

Chewing Gum

Some patients are unable to tolerate oral intake postoperatively due to nausea/vomiting and abdominal discomfort. Sham feeding with chewing gum could be an alternative. Chewing gum mimics the cephalic phase of digestion, stimulating the cephalic-vagal reflex to increase motility [34]. In older ERAS guidelines, gum chewing was recommended [25]. However, the latest guidelines do not include this recommendation after a Cochrane review concluded that evidence is uncertain due to small poor-quality studies lacking blinding [27]. Chewing gum in a RCT has since reduced POI incidence after open or laparoscopic colorectal surgery from 22 to 6% compared to standard care [15]. With regards to MIS in particular, patients chewing gum after laparoscopic colorectal resection showed shorter times to flatus, defecation, and feeling hungry but no difference in the length of stay (LOS) in hospital compared to the control group [34].

Acupuncture and Electroacupuncture

Acupuncture after open or laparoscopic colorectal resection significantly reduced time to flatus and defecation compared to sham acupuncture or no acupuncture in a meta-analysis [35]. However, existing RCTs have poor methodology quality with the high risk of bias and lack of blinding. A recent RCT comparing electroacupuncture at ST36 (on the lower limbs) or ST25 (on the abdomen) to no electroacupuncture after laparoscopic colorectal resection found that time to flatus and defecation were significantly shortened with electroacupuncture at ST36 [36]. Another RCT found that transcutaneous electrical stimulation at acupoints on the lower limbs resulted in 32% lower risk of POI and shorter times to flatus, defecation, and normal diet after open or laparoscopic colectomy [37]. POI incidence was reduced but did not reach statistical significance. After multivariate-unadjusted analysis for laparoscopic surgery, POI incidence was further reduced. Acupuncture is low cost with low incidence of adverse events and therefore warrants further evaluation for its potential role in preventing POI.

Vagal Nerve Stimulation

Vagal nerve stimulation (VNS) activates the cholinergic anti-inflammatory pathway [8]. An early development study investigating self-administered noninvasive VNS before and after colorectal surgery found the treatment was considered acceptable and time to GI-2 outcome and tolerating solid diet were shorter [38]. A RCT-evaluating low-intensity transcutaneous auricular VNS 20 min prior to anaesthesia induction for laparoscopic colorectal resection showed a significant reduction in POI incidence from 20 to 6.25% [39]. However, vagal nerve innervation decreases along the gastrointestinal tract and is almost absent in the distal colon, so VNS may have less applications in colorectal surgery than other abdominal operations [8].

Use of Analgesia

Multimodal Analgesia

Administration of any intravenous opioids within 48 h postoperatively was identified as a strong predictor of PPOI after colorectal surgery [40]. Multimodal analgesia aims to provide analgesia while avoiding opioids to reduce opioid-related adverse effects, including POI. However, it is also reported that opioid-based patient-controlled analgesia (PCA) has no association with POI after laparoscopic colectomy [4]. The inconsistent association between perioperative opioid consumption and POI indicates there are other important mechanisms underlying POI pathogenesis.

Epidural Analgesia

Epidural analgesia (EA) is considered the gold standard in patients undergoing open colorectal surgery, but its role in MIS is less clear [27]. Case-matched analysis comparing EA to conventional analgesia after laparoscopic colectomy found no difference in POI rates, while the EA group had higher costs and longer LOS [41]. Furthermore, EA was identified as a predictor for PPOI after laparoscopic colorectal surgery [40]. In a RCT, EA slowed the return of bowel function and increased LOS after laparoscopic colorectal surgery compared to spinal analgesia or standard PCA [42]. In a meta-analysis of 492 patients, EA shortened the time to first defecation after laparoscopic colorectal surgery compared with PCA but made no significant difference to POI incidence [43].

EA is associated with complications such as hypotension and analgesic failure [27] and does not provide advantages for bowel function after MIS compared to less invasive analgesic modalities. The most recent ERAS guidelines agree and favoured other methods of analgesia for laparoscopic colorectal surgery such as lidocaine infusions and transversus abdominis plane blocks (TAPBs) [27].

Transversus Abdominis Plane Blocks

In a TAPB, local anaesthetic is injected between the transversus abdominis and internal oblique muscles to provide a regional abdominal block. In one RCT, TAPBs decreased pain scores, opioid use, and LOS and resulted in earlier time to flatus and mobilisation after laparoscopic colorectal surgery compared to the placebo. However, POI incidence was not measured [44]. Research to determine the optimal TAPB placement, and the type and dosage of analgesia could enhance these benefits. Future studies should aim to establish their effect on POI incidence.

Local Anaesthesia Infusion

Local anaesthetic infusions in open and laparoscopic colorectal surgeries have reduced opioid requirements and time to tolerating solids but made no differences in the time to defecation or POI incidence compared to controls [45]. A meta-analysis reported reduced postoperative pain and accelerated bowel function return in patients receiving local anaesthetic infusion after laparotomy but not after laparoscopic surgery, indicating wound infusion is of less benefit in MIS [46]. Although local anaesthetic infusions may promote bowel recovery after open colorectal surgery, they do not demonstrate the same benefits for MIS.

Intravenous Lidocaine

Meta-analysis of nine RCTs demonstrated that intravenous lidocaine, compared to the placebo, is associated with earlier bowel movements, significantly reduced POI risk (OR 0.32), and shorter LOS but no significant difference in postoperative opioid consumption after open or laparoscopic colorectal surgery [47]. This suggests opioid sparing is not the only mechanism underlying improved bowel function with the use of intravenous lidocaine. Subgroup analysis revealed no significant differences in POI incidence between laparoscopic and open surgery. Lidocaine could be a valuable component of multimodal analgesia, but further studies should make comparison to other modalities of analgesia and investigate its effects with regards to MIS.

Acetaminophen

Intravenous acetaminophen used as an adjunct to PCA after open and laparoscopic colorectal surgery reduced POI rates from 22 to 2.1%, decreased postoperative opioid consumption, and quickened return of bowel function [16]. Intravenous acetaminophen could be easily incorporated into postoperative care protocols and its applications in MIS to reduce POI should be further evaluated.

Pharmacological Interventions

Nonsteroidal Anti-inflammatory Drugs

Nonsteroidal anti-inflammatory drugs alter the inflammatory response and may decrease opioid requirements. Preoperative intravenous meloxicam prior to open or laparoscopic colorectal surgery decreased the time to bowel sounds, flatus, and defecation, shortened LOS, decreased opioid consumption, and reduced incidence of opioid-related adverse events, including POI (3.7 vs. 17.9%), compared to the placebo [17]. Nonsteroidal anti-inflammatory drugs have shown benefits for accelerating the return of bowel function after colorectal surgery compared to the placebo, but evidence for their use in MIS is lacking and comparisons with other analgesia should be investigated.

Alvimopan

Alvimopan is a peripherally acting μ-opioid receptor antagonist that is FDA approved for accelerating gastrointestinal recovery after small or large bowel resections. Since alvimopan is peripherally acting, it enables analgesic effects of opioids at central receptors but minimises opioid-induced bowel dysfunction [48]. There has been much research on alvimopan use in open surgery, but its role in MIS is still being established. Opioid antagonists may be of less use in MIS settings where opioid use is already reduced compared to open surgery. Addition of alvimopan to a standard recovery pathway after laparoscopic colectomy shortened the LOS and lowered POI rates from 20 to 2% [18]. Furthermore, meta-analysis identified a 75% relative risk reduction for developing POI with alvimopan use in laparoscopic colon surgery compared to the placebo [48]. On the other hand, case-matched analysis found that alvimopan resulted in no differences in POI rates, LOS, or readmission rates after laparoscopic colectomy compared to controls [19].

Prucalopride

Prucalopride is a 5-HT4 receptor agonist which can activate the intestinal cholinergic anti-inflammatory pathway [8]. In a phase II RCT consisting of 110 patients, oral prucalopride after open and laparoscopic gastrointestinal surgery significantly shortened the time to defecation and flatus and decreased the incidence of POI lasting >5 days, compared to the placebo. However, subgroup analysis revealed that results were not statistically significant in laparoscopic surgery [49]. However, postoperative administration of prucalopride in a murine model of POI failed to prevent intestinal inflammation and POI, while preoperative prucalopride significantly reduced inflammation and increased GI transit compared to the placebo [8]. There need to be further trials evaluating preoperative prucalopride administration to prevent the inflammatory response rather than trying to suppress it postoperatively.

5-HT3 Receptor Antagonists

RCT comparing 5-HT3 receptor antagonists, ondansetron, tropisteron, and palonosetron, to saline in a mouse model of POI identified that 5-HT3 receptors were expressed by peritoneal macrophages, and these macrophages became adhered to the intestinal wall in the model of POI. 5-HT3 receptor antagonists inhibited macrophage infiltration, which prevented intestinal inflammation, restored gastrointestinal motility, and ameliorated POI [9]. Ondansetron also inhibited mRNA expression of inflammatory mediators. 5-HT3 receptor antagonists should be further investigated for preventing POI with the initial human trials.

Dexmedetomidine

Dexmedetomidine is a selective α-2 adrenoceptor agonist with analgesic, sedative, and sympatholytic properties [50]. Sympathetic hyperactivity is implicated in POI pathogenesis, so dexmedetomidine may have a role in preventing POI. Perioperative dexmedetomidine in laparoscopic colorectal resections significantly decreased the time to flatus, defecation, and resuming normal diet, shortened LOS, and improved haemodynamic stability compared to saline [50]. Furthermore, serum levels of diamine oxidase and intestinal fatty acid-binding protein, markers of intestinal ischaemia-reperfusion injuries, significantly increased in patients receiving saline but did not in patients receiving dexmedetomidine. Administering dexmedetomidine with ropivacaine in a TAPB prior to laparoscopic colectomy significantly decreased the time to defecation (3.3 ± 1.4 vs. 4.2 ± 1.7 days) and resuming oral diet (2.9 ± 1.1 vs. 3.6 ± 0.8 days) compared to ropivacaine TAPB alone in a RCT including 60 patients [51]. Future studies should investigate the relationship between dexmedetomidine and POI incidence.

Acetylcholinesterase Inhibitors

Acetylcholinesterase inhibitors prevent acetylcholine breakdown to increase acetylcholine concentration, which increases peristalsis and could activate the cholinergic anti-inflammatory pathway [52]. A stage 2B study showed that oral pyridostigmine, an acetylcholinesterase inhibitor, was safe to use after colorectal surgery and concluded that its efficacy for preventing POI should be investigated in an adequately powered RCT [52].

Calcitonin Gene-Related Peptide Receptor Antagonist

There have only been preclinical studies evaluating calcitonin gene-related peptide (CGRP) antagonists. CGRP was found to be released from myenteric neurones in response to intestinal manipulation (IM) in mice which aggravated the proinflammatory response, activated peritoneal macrophages, and inhibited anti-inflammatory cytokine expression [7]. Preoperative administration of CGRP receptor antagonist, BIBN4096BS, prevented IM-induced inflammation, reduced IM-induced leucocyte influx, and restored gastrointestinal motility in mice. These results indicate that future human trials are warranted.

Other Interventions

Gastrografin

Gastrografin is a water-soluble contrast medium. Due to its hyperosmolarity, gastrografin forces fluid from the bowel wall into the lumen which could reduce bowel oedema and relieve POI [53]. Two trials investigated gastrografin as a rescue medication for patients suffering from PPOI after open or laparoscopic colorectal surgery. The first identified shorter duration of PPOI in patients receiving gastrografin compared to placebo, but it was not statistically significant [53]. Gastrografin significantly shortened the time to lower tract function recovery (time to flatus, stool, and resolution of distension) but not upper tract function recovery (time to tolerating oral diet and resolution of postoperative nausea or vomiting). This may be due to anatomical and physiological differences between the upper and lower gastrointestinal tract that mean gastrografin is more effective in resolving oedema and promoting motility in the lower gastrointestinal tract. The second observed that PPOI duration, LOS, nasogastric tube use, and time to flatus, defecate, and oral intake were shorter, but the differences were not statistically significant [54]. It is possible that the trials conducted so far were underpowered to identify statistically significant differences in PPOI duration. Although not significant, there are trends toward earlier bowel function recovery in patients treated with gastrografin which warrants further investigation in larger trials.

Bowel Stimulation

POI is the most common postoperative complication following loop ileostomy closure; therefore, POI should be addressed in this group specifically [20]. When a stoma is created, the defunctionalized segment of bowel undergoes structural and functional changes, which can result in bowel dysfunction [21]. Bowel stimulation via the efferent limb of the ileostomy may aid in reversing these changes to improve outcomes after ileostomy closure. Two RCTs investigating bowel stimulation via the efferent ileostomy limb with physiological saline or thickening agents before loop ileostomy closure both demonstrated lower POI rates and shorter LOS compared to no stimulation. POI incidence was reduced from 20 to 2.85% and 24.5–6.4% in the respective trials [20, 21].

Limitations

This review has several limitations. The literature search was limited to articles available in English and full text, which may exclude relevant studies. Significant heterogeneity exists between studies due to variation in ERAS protocols, comparator arms, and POI definitions which limits conclusions that can be drawn. Blinding was absent in several included trials, and some were not randomised, which makes them vulnerable to bias. Many studies used measures of bowel function return, such as the time to defecation and tolerating solid diet, but did not report POI incidence, which makes comparison between interventions difficult. Multiple studies did not distinguish between open and MIS, despite being distinct surgical approaches with different physiological effects on the colorectal tract. This meant, at times, evaluating the effect of interventions on POI after MIS specifically was not possible.

Future Recommendations

Several of the discussed interventions have shown small but statistically significant effects on POI incidence and/or bowel function recovery. These should continue to be investigated in future studies, but these must include larger sample sizes, transparent and robust methodology, and standardised outcome reporting in order to accurately evaluate the effect on POI incidence. Future trials should report POI incidence using widely accepted definitions like the definition set by Vather et al. [2]. This would tackle the significant variation in terminology used to describe POI and the lack of distinction between physiological POI and prolonged POI that leads to inaccurate incidence reporting. Furthermore, it would overcome the challenge of comparing studies with differing outcomes. Additionally, establishing a better understanding of the physiological mechanisms underlying POI may aid in identifying novel interventions to target pathways implicated in the pathogenesis of POI. This should include investigating the precise dysmotility patterns that occur in POI.

The introduction of MIS and ERAS programmes show significant benefits in reducing POI and promoting postoperative bowel function. Reviewing perioperative analgesia methods revealed that epidural analgesia is not beneficial for preventing POI in MIS, so, given its potential risks, other analgesic modalities should be favoured. TAPB and lidocaine infusions could promote the previous return of bowel function with lower risk of adverse effects. Many other interventions demonstrated the potential to improve postoperative bowel function and prevent POI. These include VNS (by electrical stimulation, gum chewing, or early postoperative feeding), acupuncture, and several pharmacological interventions including alvimopan, dexmedetomidine, and 5HT-4 receptor agonists. Additionally, the impact of coffee drinking, CGRP antagonists, and gastrografin has not been established and warrants further research. Overall, several individual interventions showed benefit and incorporating these into a multimodal approach will have the greatest impact on minimising POI after minimally invasive colorectal surgery. However, future research should aim to use standardised POI definitions and outcomes to enable comparison between studies and should distinguish between open and MIS approaches so that accurate conclusions can be drawn about the effect of interventions on POI incidence after minimally invasive colorectal surgery.

The authors have no conflicts of interest to declare.

No funding was received to assist with the preparation of this manuscript.

E.K.A: search, data collection, data interpretation, manuscript writing, and produced the final manuscript. E.H.A: conception, guided data collection, editing drafts, and produced the final manuscript.

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