Posted on Authorea 26 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162730098.86478422/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. atclryoits lyacnrlrl.Teamo hsrve ril st ecietepae fthe of phases the describe to is colorectal article in review patients this of a of drugs, 25% and analgesic aim phase which as The during neurological high role. phase early as ”pharmacological” central an a be a phases, add can two play could has and we opiates, POI which high particularly to view, remains phase, of ileus inflammatory in point later advances POI pathophysiological Despite Numerous POI. prolonged a decrease failure. From of to renal surgery. possible rate functional it can acute the made POI have or this, rehabilitation, of inhalation early consequences bronchial particularly The management, surgery. as peri-operative abdominal such after serious complication potentially frequent be a is (POI) ileus Post-operative Abstract Acknowledgements: sectors. not-for-profit Funding: interests: competing Potential France; 3, Cedex 31024, count Toulouse Word 60039, CS Purpan, Toulouse France. CHU Toulouse, Baylac, Hospital, University Toulouse Centre), unit, surgery * Hospital colorectal (University surgery, digestive Purpan of CHU Department Toulouse, 2- of University ENVT, France. INRAE, Toulouse, INSERM, IRSD, 1- Buscail Etienne Perspective Pharmacological a Ileus: Post-Operative the of Pharmacology. and two phases J. trials the has Br. clinical describe targets. POI to published pharmacological view, is potential through of article for available review areas during point currently research phase this treatments pathophysiological different “pharmacological” of pharmacological the a a aim discuss the From add The to analyse could finally role. we surgery. to central which colorectal POI, a remains to of play in ileus phase, management, opiates, pathophysiology POI inflammatory patients particularly peri-operative prolonged later of drugs, of a in 25% analgesic rate and advances which phase the as potentially Numerous neurological this, high early Despite be as an POI. can failure. phases, decrease be POI renal to can of possible functional and consequences it acute The high made have or surgery. rehabilitation, inhalation abdominal early bronchial particularly after complication as frequent such a serious is (POI) ileus Post-operative Abstract 2021 26, July 2 1 Buscail Etienne Perspective Pharmacological a Ileus: Post-Operative nemU1220 Inserm Toulouse Centre Hospital University orsodn Author: Corresponding hsrsac eevdn pcfi rn rmayfnigaec ntepbi,cmeca,or commercial, public, the in agency funding any from grant specific no received research This 81words 6891 : 1,2* 1 C´eline Deraison , n eieDeraison Celine and hnst itraMlnv o e novmn ncneto fFgr 2. Figure of conception in involvement her for Milanova Viktoria to Thanks r ten UCI,M,PD NEM M-20 RD lc uDr. du Place IRSD, UMR-1220, INSERM, PhD, MD, BUSCAIL, Etienne Dr. oato a n oflc fitrs odeclare. to interest of conflict any has author no 1 2 1 [email protected] Posted on Authorea 26 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162730098.86478422/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. otprtv atonetnlDsucin(OD IFE cr ? 6) [?] score (I-FEED (POGD) Dysfunction and present drinking gastrointestinal They tolerate Postoperative surgery. patients - tube. of after nasogastric majority hours The a 48 bloating. nausea require and experience not vomiting to do non-bilious begin volume small but initially, nausea, well with 3-5) do of usually score patients (I-FEED These POGI intolerance gastro-intestinal hours operative 24-48 Post first the - with in difficulties non-pathological feeding transient considered are experience surgery. PONV may (PONV). following but vomiting diet, and symptom-free nausea a postoperative tolerate category this in Patients therefore 0-2) of was score system (I-FEED classification Normal - three-category physical tole- Emesis, A criteria: A nauseated, “I-FEED”). Feeling following 2018). (Intake, symptoms the ileus al., of using of established: et signs basis duration disorders(Hedrick physical functional and vomiting, transit nausea, and Examination gastrointestinal ingestion, pathophysiological oral postoperative a of definition for on rance functional system clinical more proposed After a grading and was Recovery considered semiological a Enhanced classification which for the and Consensus Society Joint standardise POI Perioperative American and the of the definition and include study a works (ERAS) propose Recent Surgery to ileus. 2014). resumption postoperative al., out of the et carried of framework Bree is 2019). been out (van treatment al., have studies defecation POI et (69 studies first of 30%)(Chapman stools Several the effects 217, first with pharmacological of the combined the out of food assess passage studies solid 64.5%), 73 to (65 of frequency, movements 217, of outcome not of intestinal of total accepted is order out first a commonly decreasing studies complex the identified The in (140 by articles motor Thus, gas followed 215 2019). migrating first 31.8%) indicative of al., the not 217, the review et function. of is transit(Chapman literature of passage normal auscultation normal recent find: to return at of a we return peristalsis the return Nevertheless, the of the transit. that define defining perception normal fact criteria to i.e. to function, used the return normal frequently a in explains to most of function lies return is motor a definition gas of with recovery and the synonymous from to stool Small of motility difference extent. first colonic time complexity equal and the The to hours The of 1994). 48 affected al., passage to are et 24 the segments from post-surgery(Benson why all motility hours Not gastric 72 peristalsis. hours, to 24 in 48 within halt peritoneal disrupted complex a the is many and motility involves of transient tract intestine reaction to digestive opening lead This the which reaction. the of of chain all Indeed, paralysis a mechanisms, surgery. pharmacological trigger and tract abdominal hydro-electrolytic digestive inflammatory, in neurological, the situation of manipulation iatrogenic and an cavity is ileus Postoperative Definition paralytic al., POI. all et reduce (Solanki for POI or pharmacological 2011 prevent the costs of in to and Pathophysiology care dollars development POI total for billion under responsible annual 12.3 or mechanisms employed to the on currently 2001 knowledge USA, strategies current in the addresses dollars stays. review In hospital billion This of 7.1 considerable. 2020). length from are the increased prolongs POI et hospitalisations and (Chapman morbidity with ileus own surgery associated its abdominal following induces costs patients (POI) varies The of ileus and 25% postoperative frequent and The extremely or 10% is 2018). deceleration between complication al., a affecting This series, reflecting 2020). the and al., to surgery et (Venara according abdominal motility after intestinal in occurring arrest condition complete common a targets. is pharmacological ileus potential Postoperative for published areas research through different available the currently Introduction discuss treatments to pharmacological finally the and analyse trials clinical to POI, of pathophysiology 2 Posted on Authorea 26 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162730098.86478422/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. neatdrcl ihnrefirs iha diinl2%lctdwti m(unre l,21) It 2017). al., et (Buhner cells mm mast 2 mucosal of within 70% located about submucosal 20% and and additional cells mucosal an mast endings the mucosal with nerve in with afferent fibres, found contact Extrinsic (Echtenacher nerve close are layers. increased with in cells serosal is are directly and mast sepsis neurons interact muscular of enteric the bacterial number as in to and greatest well represented vascular due as the less in are mortality intestine, have role they the cells, models whereas regulatory In mast layers, peritonitis a murine in play 1996). in deficient cells al., studies anaphy- mast animals et Indeed, and tract, in allergic particular. digestive that, in in the defence shown effectors In immune as and 2008). especially permeability al., activate phenomena, epithelial et immunological turn, (Galli in in processes involved trigger lactic mechanisms which, are targets. these (MCs) proteases pharmacological of cells potential and All Mast constitute histamine functions. and barrier of ileus intestinal postoperative secretion alter accompanying with and inflammation leukocytes cells and mast macrophages of resident activation involves POI. the This surgical of the nature phase by prolonged inflammatory generated potentially inflammation late abdomen the local The the cease. explains and will which of pathways damage begin, traction these tissue then of manipulation, the will activation intestinal postoperative to completed, procedure by secondary immediate been cascade stimulation the have inflammatory laparoscopy in and for An and closed distension procedure is and surgical laparotomy abdomen the for the during Once peak 1996; its period. al., reaches et phase (Barquist neurological synapses inhibition This (VIP) another activates vipergic nerves and 1999). splanchnic (NO) (Boeckxstaens the al., nitrergic nerve of via et vagal stimulation system the Boeckxstaens noted Intense motor of digestive activation be 2017). the to al., should of factor leading pathway et pathway, releasing It Browning activation nucleus Corticotrophin 1999; this the 1997a). hypothalamus. al., in is al., et as the role et bowel Winter central such of nature(De a the in nuclei nuclei plays adrenergic when (CRF) supraoptic also pontine-medullary and are phase, and and relays brainstem(Fox 1985; neural paraventricular neurological hypothalamic the these Powley, the that second by to and and activated the relay tract(Fox solitarius are pathways In digestive tractus pathways These entire the additional 2018). in the intensely, 1985). Cirillo, nerves of more Powley, efferent and stimulated paralysis activates Vergnolle and signal in 1996; This manipulated resulting al., neurons. tract et adrenergic digestive with Barquist afferent the cord splanchnic via spinal of arc the reflex direction neurological in a synapse causes selective laparotomy that during nerves peripheral incision by peritoneal and mechanism muscle POI Skin, (De this of transit with phase GI Interference of neurogenic in later. early types reduction detail 2002). The different in a Kehlet, discussed after and and be neurons analgesics will myenteric Holte as antagonists from 1997b; opioid used release al., often acetylcholine of et activation of Opioids, phase the Winter inhibition This through to motility opioid. apparent. GI leads neural also of on This is involving impact use phases major phase the previous a two have early by surgery, features. the an conditioned inflammatory to by ”parallel” essentially - characterised occurring is POI phase, phase later pharmacological in a third phases and A not phase”, two will “neurogenic least ileus the Secondary at as known 2018). identified surgically.pathways, al., have managed et usually studies (Chapman is treatmentsPathophysiological it administered aetiological as are which here sepsis complication for surgical with of a complication dealt treatment by septic be caused causal is postoperative the but another symptoms on same or based the fistulae by aspiration. defined anastomotic is prevent is as This treatment to maintainsuch essential Specific occur. to also also necessary can is ingestion. POI are tube Secondary oral balance and nasogastric electrolyte to A nausea and intolerance fluid function. most resistant with of by renal anti-emetic associated maintenance ileus proper tympany, and considered is hydration is with This Intravenous what distension to required. vomiting. corresponds abdominal bilious and develop volume recovery patients GI large impaired These of form severe clinicians. most the is POGD 3 μ- podrcposo ynei fibres. myenteric on receptors opioid Posted on Authorea 26 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162730098.86478422/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. h ehnssadatvto fteiflmaoyptwyadrsdn arpae lctdi the in (located macrophages resident and pathway inflammatory nerves spinal the afferent of the activation smooth stimulating 2019). contractile and Forsythe, PG inhibit 2010; mechanisms of phenomena al., The secretion These et (iNOS) 2003). the Cenac synthase al., by 2007; oxide et al., production potentiated nitric Kreiss et (PGs) further (Grant inducible 2000; prostaglandin is and al., of which (NO) et regulation activity, oxide Kalff up- muscle nitric 1999; to increased al., leads in et cells resulting (Eskandari (Kalff (COX2) these diapedesis 2 of by cyclooxygenase invasion muscularis and intestinal The the 1999b). into al., lym- leukocytes, (ICAM-1), et particularly molecule-1 cells, (T adhesion pro-inflammatory endothelium (intercellular of che- the molecules passage of in adhesion antigen-1(LFA-1)) cell production function-associated of the up-regulation (TNF phocyte in an alpha in resulting Factor protein-1 results reactions necrosis and inflammatory of (Tumor macrophage cascade cytokines (MCP-1), a pro-inflammatory protein-1 to chemoattractant leads (monocyte are macrophages mokines there resident quiescent are of that they activation fact bacterial, physiological The the notably In aggression, despite generate. 1999a). infectious ileus they al., or mechanisms postoperative stress et the inflammatory in (Kalff and (Kalff any role pathway plexus of activation predominant the mesenteric outside their the of central, conditions, near regarding phase a muscularis areas inflammatory the play unknown the in They still of housed 1998). are pin macrophages lynch al., These the et 2015). are to al., pathway et permeability activation (Asano paracellular et their ileus in 2008; (Jacob and increase macrophages MCs al., an resident by and et with The secreted junction interaction (Hyun tight mediators the by enterocytes - 2012). of tryptase regulated the al., redistribution (Mart´ınez and partially of in et chymase macromolecules results is part by This activated function basolateral 2005). also barrier the al., into is This bacteria on PAR-2 of (PAR-2) 2016). passage 2001). receptor-2 Vergnolle, the macrophages. al., activated in resident et to results protease of alteration (Santos activation the leads its for propria activation because pathway lamina element vascular potential MCs regulating important the a in an being role is 2010). major latter permeability a the al., Epithelial play function, substances bidirectional heparin, et These barrier via (histamine, epithelial stored 2016). (Cenac signals and and al., nociceptive mediator) system et are (Wouters lipid of pathways substances nervous and activation active (cytokines These the enteric synthesised proteases) newly in the of role 1994). as release such a of and al., hormones degranulation play or transit neurons et also 2004) decreases al., MCs with Zittel et are antagonist 2014). (Barreau interactions 1993; MCs (NGF) al., CGRP factor section. al., et growth targets” a (Vanuytsel nerve et ”potential as CRF the of such (Plourde in factors use detail growth ileus in by the discussed activated of also be Indeed, will model and murine targets inflammatory procedure. pharmacological and the a prospective surgical in P involved in a are substance time two after latter recovery as The response such 2014). motor al., neuropeptides neurotransmitters et and by (Wang and activated (CGRP) epinephrine) be peptide MITF gene can dopamine, AP-1, express calcitonin-related MCs as also serotonin, pathways, such MCs non-immune histamine, factors Regarding . (acetylcholine, of 2006) 2006). transcription Gilfillan, Gilfillan, and and and (Rivera (Rivera phosphorylation (Fc production and of IgG cytokine cascade immune for and a receptors between degranulation to surface-bound to made cell leads and STAT-5, be of This Fc and can cross-binding receptor 2008). the distinction high-affinity al., is its a activation et to and MCs (IgE) for multiple E stimulus are immunoglobulins classical cells The mast pathways. emptying gastric non-immune of reduced pathways ileus: and activation layer) of muscle The model 2004). the murine in al., particularly, et a immun- more myeloperoxidase Jonge in and, by (de these Doxantrazole wall Jonge (measured time ileum and inflammation of De entire reduced Ketotifen the consequence molecules in as both 2008). direct odetection such with al., mice a stabilisers the et cell is of dysfunctions pre-treatment mast (The motility neuromuscular of ileus digestive and administration in postoperative epithelial the triggering generates Alteration cells potentially hypersensitivity. mast phenomena, of visceral activation promotes that and fact well-established a is γ I,ohrI-soitdrcpos opeetfato n ollk ufc receptors surface toll-like and fraction complement receptors, Ig-associated other RI), 4 ε Ib nalre nasniie niiul(Galli individual sensitised a in allergen an by RI α ,itrekn IL1 interleukin: ), re ta. 07.Ti eut nthe in results This 2007). al., et urler ¨ β, tal et L)adintegrins, and IL6) investigated . α (MIP-1 α )), Posted on Authorea 26 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162730098.86478422/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. ueo vr3hus uain(hpi ta. 2013). al., proce- et surgical (Chapuis of and duration history history, placement hours’ vascular 3 stoma peripheral over be transfusion, gender, of cannot intraoperative male dure surgery, were studies POI in emergency of identified pathology, predictors those respiratory independent of The many however surgery. cancer ileus, postoperative Chapuis for factors modified. risk several are There the and inducers, Treatments (iNOS) Non-Pharmacological macrophages synthase resident al., oxide by et production nitric (Frantzides NO contraction. inducible decreases doses and are models 1998). murine bursts higher opioids and (Kowalski, in non-propagating at addition, antagonist) primate (mu-receptor random, observed In naloxone on of of were 1995). use frequency contraction studies al., the and (digestive et Previous of in Ferraz activity range ileus increase 1992; myoelectric dose 1995). of an morphine colonic was a signs al., of there at functional Inhibition et that, ug/l, shown (Ferraz the 200 have to of 1998). activity 50 myoelectrical etc.) symptoms (Kowalski, colonic enteric emptying, secretion to investigating of acetylcholine physiology gastric inhibition leads clinical and is and of opioids oxide activity inhibition of nitric action motor P, distension, of propulsive substance level first inhibits of The This inhibition tract. with gastrointestinal activity Exogenous the The on nervous at 2009). effects 2008). primarily the Blum, (Thomas, act for and system codeine vectors Becker nervous and being morphine peripheral 2005; ones as and al., main such central et three as the (Gonenne such receptors, agonists exogenously mesenteric opioid opioids and the of endogenously from tract types stimulated gastrointestinal several acetylcholine are the are of in There release activity 2004). δ, propulsive motility the Delaney, μ, reducing gut 1986; inhibit and al., postoperative analgesics tone et inhibiting muscle opioid (Schang in colonic other role increasing predominant and peripheral thereby a and plexus, Morphine central have a receptors 1). is gastrointestinal (figure which but morphine, POI, is the anaesthesia of and analgesia for al., drug µ et used Wehner commonly 2005; most The al., et Jonge de leading factors 2003; (EGR-1) Pharmacological al., 1 et kinases protein (Hommes of response genes activation growth signal pro-inflammatory (RAGE) (NF-kB), 2009). early the of product kB and involving transcription (STATS), factor end pathway the nuclear transcription glycation signalling as to of such advance intracellular activator All factors for an and transcription (TLR). receptors of generates transducers Receptors phosphorylation and This Toll-Like causing TLR JNK/SAP) with 2001). of (p38, interact activation al., altered, liposaccharides to et is barrier as lead (Hori intestinal such phenomena the of when products these release Finally, the their of 2007). al., to or (DAMPS) et led invasion patterns (Lotze pathway manipulation molecular bacterial another damage-associated intestinal 2011). is by by Activation damage al., cellular caused et IL-1alpha. during and (Rosas-Ballina tissue HMGB1 ATP, cells intestinal as T of such regulatory factors dehydration by of and induction (Ach) damage and acetylcholine Tissue production of 2006) al., secretion et The (Huston 2020). TNF route of resident al., another activation and to (7 constitute et leads neurons receptor efferences, pathways enteric (Stakenborg vagal between the by cholinergic plexus stimulated proximity in intestinal neurons, to myenteric is enteric debated The appears the There been CGRP 2015). macrophages. in has Indeed, and al., cells) macrophages 1997). neurons et (mast al., between pathway (Glowka et interaction this study Rekik of although 1997; recent cells, al., of mast et light and (Bueno gene-related macrophages (SP) calcitonin pro-inflammatory resident P of of activate role substance release the the and highlighted to have (CGRP) studies leads Numerous peptide fibres evidence. 2020). afferent of al., of levels et activation varying (Stakenborg intense with neuropeptides via multiple phase are neurological layer) muscle initial circular The and longitudinal between plexus myenteric eetraoit(eWne ta. 97) hscnrladprpea cincnrbtst prolongation to contributes action peripheral and central This 1997c). al., et Winter (De agonist receptor and κ eetr,wt ahcasas aigsvrlsbye Sabza ta. 02.Oii receptors Opioid 2002). al., et (Shahbazian subtypes several having also class each with receptors, α CR d og n lo,20) hs ciaino h 7 the of activation Thus, 2007). Ulloa, and Jonge (de AChR) tal et odce nosrainlsuyivlig240ptet negigcolorectal undergoing patients 2,400 involving study observational an conducted . 5 μ- eetr fteetrcsse r h main the are system enteric the of receptors α -utp ftenctncacetylcholine nicotinic the of 7-subtype μ- eetr hc r rsn nthe in present are which receptors α CR’ edn oihbto of inhibition to leading ’s AChR Posted on Authorea 26 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162730098.86478422/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. or otsreysoe infiatrdcini h iet ne ftefis atonetnlmove- gastrointestinal first the of onset 24 to treatment time of the initiation cohort a with in in n=55) reduction study mg/day; significant 2 (2 phase a prucalopride A or showed (n=55) results. post-surgery its promising placebo hours test more receiving show to patients underway to 110 currently appear emptyingof is prucalopride gastric involving trial the studies clinical improved Clinical A TAK-954 with 2021). and treated (NCT03827655). al., events group POI et control adverse on (Chapman efficacy a in metoclopramide feeding TAK- to difference to enteral agonist, compared with compared no receptor was patients rate was 5HT-4 ventilated administration novel mechanically TAK-954 There a of with of cohort group metoclopramide. safety a Chapman study and in Recently, The efficacy time the emptying intolerance. 2011). assess gastric al., to improving trial 2011). in et thus clinical 954, al., macrophages(Tsuchida and 2a active et secretion phase (Toyomasu acetylcholine on a of defecation conducted receptors activation first 7nAChR via and of colectomy properties activation faltus elective anti-inflammatory first underwent had a who to manipulation had intestinal patients time group 30 mosapride the vs. of the in Tsuchida However, study Interestingly, mosapride improvement 2008). cohort significant comparing al., Another a study et showed stay. (Narita cohort recovery hospital selective A transit of shorter actions of the significantly 1). the duration stimulate (Table of the to one in prucalopride be improvement is Narita and would This by nerve mosapride tract. conducted vagus digestive as placebo the the such along of agonists neurons action enteric 5HT4 the from have ’mimic’ 2005). acetylcholine context al., of could this and release et that in dopamine Chan alternative cohorts 2001; antagonising pharmacological for patient Kale-Pradhan, to drug A small and attractive addition involving (Seta an studies In results it However, conclusive making produced 2021). ileus. receptors, not 3 postoperative al., type of et gastric serotonin treatment (Isola against of the acts jejunum acceleration also resting and increasing metoclopramide to the thereby duodenum apomorphine, sphincter, increases leads pyloric the also the It This relaxing in simultaneously of contractions. while peristalsis sphincter oesophageal inhibition 1970). oesophageal of lower the duration the the Hunt, reduce of and to tone and amplitude to the system metoclopramide (Ramsbottom increasing gastrointestinal allowing by apomorphine emptying the Metoclopramide apomorphine, by 2017). of from al., emptying effects transmit et 2021). (Harada gastric antiperistaltic that zone al., trigger the nerves chemoreceptor et blocks the afferent (Isola of also area chemotherapy visceral involves postrema mechanism the of of which in The disease centre effects sensitivity metoclopramide, vomiting receptors. reflux adverse in is dopamine-2 gastroesophageal peripheral of agents in decrease and prevention vomiting used a central and the widely antagonising nausea by for most of acts the and treatment Metoclopramide the of gastroparesis, for One diabetic improvement FDA no Cochrane the and showed 2008). by a trials al., However, approved randomised been et 39 practice. and (Traut has clinical agents ileus in prokinetic vomiting 11 postoperative and of in trials nausea clinical treat comparative to of used review regularly are the agents in Prokinetic day 1 Trials” of Clinical reduction of median Prokinetics in Results a shown and with as “Mechanisms hospital Finally, Treatments: from to 2011). discharge Pharmacological return 2011). al., faster median et visceral al., al., a a prevent (Vlug et et allows and stay to (Shah (Vlug approach of earlier order leakage motility laparoscopic length day in the gut anastomotic one state patients, of and food fluid post-colectomy recovery POI tolerate 400 balanced the involving of equipment the in trial risk This of factor LAFA the monitoring the a 2012). non- the increases also al., is that is The et aspect which oedema (Vlug of early, important recovery emptying mobilised Another prophylactic transit 2011). be because in 2011). to improvement al., tube patient patient any nasogastric of et the highlighted a not ”simplification” a allows of not are (Vlug as placement has described literature, routine be particular stomach the can no the strategies in in is these there described of motility outlines Firstly, widely broad management. The intestinal schemes, rehabilitation paper. post-operative on this these the in discussed on in and measures used surgery rehabilitation measures early pharmacological abdominal of of effectiveness the course shown have publications Numerous tal. et tal et Gt21)soe namuemdlta diitaino oard ro to prior mosapride of administration that model mouse a in showed 2011) (Gut novn 0ptet h a negn lcieclcoysoe no showed colectomy elective undergone had who patients 40 involving . 6 tal. et Posted on Authorea 26 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162730098.86478422/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. ae orsm rni otprtvl Lee l,21) hs norgn eut eentmroe in mirrored not were time results the encouraging in These improvement an 2014). showed al., on reported, also et trial been cystectomy (Lee clinical the have radical postoperatively randomised events in after multicentre cardiovascular transit reduction adverse surgery A resume significant that to undergoing confirmed 2008). a wastaken patients noted were (Erowele, Alvimopan of with be results alvimopan 2007). cohort should 2) for These al., a It Table indications et in the 2020). (Delaney 2008. limiting (detailed particular al., in thereby in trials FDA et signs hospital the (Jang III functional to by clinical phase stools readmission approved with by and first three treated hospitalisation evidenced or of patients of as movements 2004; placebo, analysis duration recovery bowel to al., combined transit Compared first et a of to 2012). 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Viscusi undergone Delaney, controlled Schmidt, have and randomised (Neary 1994; who activity 2000s, al., patients gastrointestinal predominantly early et in the (Zimmerman resulting barrier Since 6% of blood-brain quaternary prevents (figure1). bioavailability and the a oral methylnatrexone absorption an crossing is and gastrointestinal from restricts alvimopan alvimopan drug antagonise that Lilly, are polarity the to Eli opioid barrier and is peripheral by form blood-brain main function zwitterionic 1994 the high-molecular-weight The bowel in cross action. postoperative not described analgesic of do central Originally recovery their that the negating used without optimising antagonists namely receptors of opioid agonist, way peripheral another one the above, with described trial As a ανταγονιστς ρεςεπτορ in οπιοιδ postoperative correlated in μ were inherent Περιπηεραλ results morbidity 2014). negative any of al., show prevention These et not (Beck the did 2013). ipamorelin patients) or al., n=330 Strasbourg time 008 et NeoMPS, recovery (ulimorelin ULISES ileus(Shaw trials and pmol/kg/min, faster transit clinical patients, al., hand, (15 in n=332 III et other improvement analogue 007 phase Bochicchio the significant ULISES other ghrelin 2010; two on studies, However, a al., safety and, 2013). et and infusing (Falk´en hand al., efficacy group(Popescu by surgery et one after placebo found the trials and the doses were on before clinical to several France) effects results IIb over compared adverse Similar shown, phase group of have two study absence route studies 1, 2012). the Table an These promising in in ulimorelin, 101/Ulimorelin, ulimorelin. a recovery shown of TZP of this transit As satiety was ug/l) safety make regulating and trials 600 receptor. agonists efficacy clinical – in GHSR1a the its in (20 the role assess used for and a to molecule affinity ghrelin play conducted first high of were afferents The a vagal properties with ileus. gastric prokinetic agonist postoperative an the The of in treatment 2005). (Gnanapavan receptors the studies al., for ghrelin expression et addition, receptors its mRNA first Roux ghrelin In and of was of (le discovery immunohistochemistry Ghrelin because 2002). the through functions by al., 2001). system supported prokinetic al., et was nervous for rationale et enteric investigated This (Cummings the later 2011). intake in alternatively was al., food two et meals, and smaller after motilin(Janssen by with hormone in to regulated decrease similarity receptor growth-releasing is produced a ghrelin a protein-coupled and also of as G level level is described The a pre-prandial Ghrelin is high 2008). mainly al., a receptor 2003). is et immunewith ghrelin GHS-R1b)(Gutierrez al., and Ghrelin and The lung et (GHS-R1a testicles, decrease variants (Dass liver, gradual 2008). spliced hormone. kidney, colon a thyroid, al., orexigenic is heart, the et pancreas, There an to gland, system)(Lutter 1999). (pituitary stomach and al., tissues et the other peptide in (Kojima from quantities mucosa acid production gastric 28-amino oxyntic its of a in cells P/D1-like is the by ghrelin produced 1999, in groups. in Discovered two ileus other postoperative the on a effect to signifi- in no compared and via having study mediated group duodenum was comparative prucalopride the effect a anti-inflammatory a in the Stakenborg the out and genes in that confirmed group pro-inflammatory observed 2016). also stimulation were of authors al., nerve The recovery expression et vagus transit the results)(Gong a faster in group, detailed cantly reduction placebo for a a 1 group, comparing Table prucalopride patients (see duodenopancreatectomy gas 30 first of the of arrival al. the and ments lgnl eosrtdteat-namtr n rkntcpoete fpuaord.I cohort a In prucalopride. of properties prokinetic and anti-inflammatory the demonstrated elegantly α nCRKokOt(O s idTp W)mdl ihprucalopride with model, (WT) Type Wild vs. (KO) Out Knock 7nAChR α nCRK ieSaebr ta. 2019). al., et mice(Stakenborg KO 7nAChR 7 μ- podrcpo naoitwt a with antagonist receptor opioid α nC eetr ycarrying by receptors 7nACh et Posted on Authorea 26 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162730098.86478422/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. n,mr motnl,t banaagsab euigteamnsrto foits ioan a been has Lidocaine opiates. analgesia of optimise administration to the is reducing time recovery by transit analgesia reduce obtain and to period importantly, postoperative more the a and, improve of to administration way the Another al., of et consideration Subendran merit treatments 2014; control septic Other al., pain or on et fistula and reluctance anastomotic Saleh time developing to inhibitor. 2012; of transit COX2 leading risk al., on selective less NSAIDs, et with results of (Gorissen patients the of use teams categories complications, the anaesthetic certain and inconsistent and in Nevertheless, reports fistulae surgical literature 2014). the postoperative the Indeed, of of celecoxib part rate NSAIDs. The of the the on use prostaglandins 2009). on routine and placebo COX the particularly al., and of to results, (n=7) et functions obstacles protective (Wattchow diclofenac are the the there given placebo However, than healing, and mucosal (n=1) 2009). ileus mg al., et postoperative (Wattchow 50 groups with diclofenac (n=9) patients fewer mg, significantly 100 had celecoxib group abdominal al., with major et undergoing daily patients NSAIDs(Tanaka it 210 twice non-selective of However, Wattchow trial although than by clinical conducted mucosa, 1991). controlled effects was randomised gastrointestinal surgery al., multicentre adverse the II et serious of phase (Xie A mechanisms fewer defence inflammation 2001). generate the in inhibitors in involved involved selective 2007). is are COX2 (Wallace, which isoforms prostaglandins damage protective COX2, both to of that and synthesis respond appears the tract, and allows gastrointestinal which further resist COX1, the have to isoforms, which in COX mucosa 1980s by two gastrointestinal mechanisms the identified the have the in studies and of The defence conducted ability mucosal Studies the to cells, contribute impair epithelial 2004). prostaglandins the NSAIDs which prostaglandins of al., maintaining by surface substance, et mechanism the for toxic digestive on (Wallace the a mediators mucus defined the to homeostasis the and exposed in bicarbonates of epithelial of is prostaglandin one preserving secretion mucosa are of the thus gastric These flow, and role the blood mucosa of When the gastric 2000). gastric rate maintain by mucosa. the help the al., gastric explained in in the et be the secreted increase of (Wallace can integrity notably an for the surgery, They are tract gastrointestinal molecules they digestive 2005). selective of Indeed, attractive the al., case including tract. the et be in inhibitors, in (Elia effects to COX or, fistula adverse ulceration However, appear anastomotic for peptic therefore include phase. responsible effects NSAIDs inflammatory are and adverse its H2 phase. inhibitors, 2007). inflammatory prostaglandin in 2 the into (Wallace, particularly COX in acid ileus, NSAIDs element arachidonic key of of of a conversion prevention target is the 2 allows the COX synthase is via G/H2 prostaglandins prostaglandin of or secretion COX the in- above, 2 described As (COX) 2013). III al., cyclo-oxygenase et phase selective Viscusi a and 2011; including al., (NSAIDs) hibitors trials, et drugs (Yu clinical anti-inflammatory 2) properties, (Table Non-steroidal antagonising results receptor conclusive generated its not Despite have trial, 2006). Israel, affinity: the and to decreasing (Yuan binding of opioid of derivative antagonises Methylnaltrexone quaternary order reduces 1982). nmol/L), and a in solubility al., is lipid et receptors reduces It (Russell polarity, barrier 1980s. opioid increases nitrogen blood-brain the to the in group of methyl Chicago crossing a of of University addition The the naltrexone. 2016; at al., developed et 2019). was inconsistent(Keller al., The are Methylnatrexone et alvimopan 2016). 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Data may be preliminary. en yoiekns y,i h ernlto fms el n ciaino eietmcohgshas macrophages pro- resident the of of activation role and essential cells series The mast complex of mediators. a degranulation inflammatory triggers the cells of mast in release on Syk, the receptor kinase high-affinity in tyrosine its resulting tein, to occurrence events bound the biochemical antigen and of level and IgE protease the procedure peritoneal by surgical the Aggregation the between 2015a). and the of correlation al., colectomy(Berd´un invasiveness and cells a et 2015a). after group the also mast al., POI cholecystectomy was between (Berd´un of of et the There correlation procedure density between activation. positive concentration surgical the cell tryptase a the mast studied and suggesting of team chymase group stages same in several colectomy difference The at a 2012). chymase was al., and There (Jard´ı et tryptases K252a proteases, (OVA)-induced ovalbumin by their oral activity prevented colonic to effect spontaneous exposure observed an upon They observed rats. alterations in contractile hyperactivity Jardi markers MCs colonic inflammatory Similarly, the of 2015b). in expression involved al., the et are are (Berd´un decreased et (TrkA)(Marshall cells and IL6 A mast cells as Indeed, kinase mast such of activation. receptor degranulation their Berdun tropomyosin prevented inhibit 2002). 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Data may be preliminary. ih2H.Teewsasgicn eraei L n L rdcini h tmltdgop compared groups stimulated the in production IL8 one and and IL6 5Hz with in the stimulated decrease in group significant enrolled one CAIP. a were stimulation, patients was without stimulate Eighteen group There to one patients. 20Hz. has explored groups: surgery approach recently with three colorectal stimulation been was into postoperative electrical divided time has This of and transit cohort opportunities study models. and a treating porcine Other inflammation in and and studied on murine hand stimulation 2016). been in one nerve studies the al., vagal preliminary on in et abdominal inflammation demonstrated electrical (Gong et promising controlling shown (Nemethova of for hand have propria efficacy cohort prucalopride other The lamina patient as such the a the Prokinetics in and on 2014). and plexus POI al., models myenteric fibres et enteric animal the Matteoli neuronal with in 2014; in cholinergic synapse results al., both between et only gut, Cailotto proximity efferents 2013; the vagal the al., in Indeed, highlighted residing have wall. macrophages studies intestinal and anatomical the However, in cells that acetylcholine neurons. immune of with secretion local contact 7 Matteoli via indirect to spleen-independent 2005). binding was al., by POI macrophages et the resident on Jonge inhibits Vagus nerve (de vagal 2014). recovery the inflammatory of al., transit cholinergic of effect faster recruitment et protective of and to stimulation Matteoli production This factors leading cytokine 2011; mice. inflammation, cells, and muscle in al., immune intestinal effective stimulation timing et in nerve decrease is the vagus The a manipulating in highlighted 2005; and by resulted have al., demonstrated muscle first et studies was smooth involvement Jonge Numerous nerve intestinal (de 2011). 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(3-45), difference mg 20 significant 18% at (12 no retention: occurring was placebo (gastric events There adverse to mg (5-75)). of compared 4 basis were time P=0.01), the Patients emptying (1-7), 50%. on second-generation of gastric mg bioavailability a 4 approximate decreased an and is It significantly has mg Ketotifen properties. and 12 intake anti-histamine group. at oral and dosed after placebo anti-anaphylactic absorbed a potent Two completely scintigraphy. almost with and is by stabiliser group measurement cell patients Ketotifen-treated transit 60 antagonist/mast involving a and H1-receptor trial clinical compared: oncology 2015). pilot were a gynaecological al., addition, in et for groups assessed In (Glowka was surgery. surgery 2) macrophages after (figure abdominal resident hours POI More undergoing in of 3 prevention receptors 1993). the externa a CGRP for muscularis al., triggering stabilisation of the MCs et models, presence in murine (Plourde the expression in to models mRNA studied refer mouse IL6 effect been authors and in has capsaicin-mediated the beta 4096BS) a described IL (BIBN addition, been antagonist in (RAMP1), In has receptor decrease 1994). 1 CGRP emptying al., protein new gastric et a focusing modifying (Zittel of recently, studies activity 2) acceleration in (figure highlighted receptor the antagonists been on via have CGRP inflammation neurons and in capsaicin afferent roles on their with and cells (CALCRL) transit. receptor-like mast faster calcitonin of significantly had interaction 2013). 143 The al., GSK et with Bree treated (van Mice macrophages (figure2). lipopolysaccharide-treated POI Bree of addition, Van model In mouse 2010). a al., in et (GSK143), (Siraganian described been in-vitro tde hwdta S 4 lce usac n erae yoieepeso in expression cytokine decreased and P substance blocked 143 GSK that showed studies α CR(atoie l,21) h au ev nycmsinto comes only nerve vagus The 2014). al., et (Matteoli AChR 10 tal. et tde h y niio,GKcmon 143 compound GSK inhibitor, Syk the studied tal. et hnsoe htthe that showed then Posted on Authorea 26 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162730098.86478422/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. ny(lecrl) pod c nm-eetr rdrcpos.Teoiishv eta nlei action analgesic central opioids a with have treated opioids is The patient receptors). a (red situation, mu-receptors this on In mechanisms act A) the Opioids antagonists. of opioid circle). representation peripheral (blue Schematic and only antagonists. opioids opioid of peripheral action and of codeine) and leu-enkephalin, (morphine (Met-enkephalin, oid opioid endogenous of Action 1: develop Figure to and phenomenon this legends of of Figure understanding source ad- a our are promote at example, to managed treatments. for essential pharmacological treatments, recurrence, be are frequent new pelvic to avenues increasingly or research recurrence These carcinomatosis New protocols. tumour peritoneal 2020). POI. rehabilitation for al., or surgery et early tumour cytoreductive (Denost and as the surgery surgery such extensive allows abdom- invasive often now Indeed, minimally through oncology essential. stages with vanced is in date progress that progress to of on-going mechanisms recent progress study and molecular However, continued made and and be has identification cellular must surgery the combined work inal of The The understanding ileus. our permeability. postoperative improve new intestinal govern develop will POI, of and during agents study observed alteration pharmacological to damage and new interesting intestinal is inflammation of mechanisms it as intimate practice, such the clinical target in that applied approaches commonly pharmacological strategies the to addition antibody In an a with in ICAM-1 manipulation as intestinal local such by Conclusion 2005). in molecules induced al., role adhesion inflammation et important reduces (The of an model 3082) inhibition play IL10 murine ISIS also that of oligonucleotide leukocytes showed However, effect antisense of al 2009). pro-inflammatory (ICAM diapedesis al., et a and et The demonstrated extravasation (Stoffels Finally, which phase inflammation. studies 2018). inflammatory recent the al., by KO of et IL10 challenged resolution (Stein with In been the model have in intestine. ileus results IL10 an the on for these of work role manipulation and in a expression surgical IL10 highlighted IL10 of after mice postoperative induction response increased temporal significantly inflammatory significant CO the the addition, during revealed musculature also external inhalation direct CO the the 2020). following using recently, al., mice studies More et in afore-mentioned Dingenen reported 2015). The (Van been al., Hemin have et action of POI-preventing (Babu administration and MAPK intraperitoneal mitogen anti-inflammatory of of p38 the its – induction mechanisms of and and kinases HO1 The phosphorylation pathway signal-regulated of via (sGC)-dependent induction (extracellular 2018). cyclase (HO1) MAPK guanine 1 al., soluble oxygenase ERK et a haem of Dingenen via Babu suppression Van by phosphorylation include depth kinase) 2009; activated level in by promising al., reviewed MAPK modulated with et and at be Backer administration described POI can been POI(De intraperitoneal have MAPKs by of action locally 2012). models CO or al., mouse et (CO) in the (Wehner reduces monoxide results POI and carbon model during (CPSI- inhaled murine oral contraction a and administering muscle in (CNI-1403) and intravenous of action Furthermore, anti-inflammatory anti-inflammatory effect its 2011). reproduces suppressant encouraging al., reproducing semapimod provided et for of (The has and administration is tract nerve POI ventricles 2364) digestive vagus cerebral of the the the on model into of action (CNI-1493) mouse stimulation motor semapimod pharmacological the of for on Injection route Work administration. one of 2016). al., routes et al., several (Bianchi via et ligands results gp96(Wang TLR by chaperone induction Wang TLR COX2 [amidinohydra- by (Wehner and the tetrakis out activation 3) decanediamide carried NF-kB (figure 5diacethylphenyl] and Studies p38MAK [3, signalling 1995). of N-bis intracellular inhibitor N, with an (CNI-1493, is interfering zone]) Semapimod by stabilised 2009). al., be et also can macrophages Resident 2017). signalling al., Intracellular et (Stakenborg group sham the to tal. et hwta eaio eestssTRsgaln i t ffc on effect its via signalling TLR desensitises Semapimod that show 11 β- tal et nopi,addnrhn,eoeosopi- exogenous dynorphin), and endorphin, h ehnsso cino Oon CO of action of mechanisms The . Posted on Authorea 26 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162730098.86478422/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. fitsia mohmsl.Tesceino C yetrcnuos tmltdb aa ffrne,leads efferences, vagal by stimulated neurons, contraction enteric by inhibiting ACh leukocytes, of and and NO secretion macrophages of The resident production by muscle. increased COX2) by smooth followed and intestinal externa, iNOS muscularis of of the into upregulation (TNF leukocytes (via cytokines of PGs influx of an release to intracellular leads and of hand This activation genes one MIP1 in pro-inflammatory the results (MCP1, TLRs on chemokines of to and liposaccharides transcription Binding and increased other. bacteria the with resident of on manipulation signals passage products Intestinal degradation response, the tissue targets. in increased inflammatory pharmacological results and potential permeability the muscle and intestinal smooth surgery increased in the abdominal and of involved following activity contractile intestine the mechanism the of of Inhibition proposed the underlying the mechanisms activation, macrophage of representation Schematic 3: modifying re- Figure TrkA, activity Fc receptor 1; receptor-like; RAMP1, receptor-2; ankyrin Calcitonin receptor-2, proteinase-activated potential CALCRL, proteinase-activated PAR2, 1; PAR2, receptor factor, protein transient factor; growth TRPA1, growth immunoglobu- nerve 1; neuronal IgE, for vanilloid 1; NGF, ceptor potential receptor receptor; receptor histamine 1 transient H1R, neurokinin TRPV1, peptide; NK1, gene E; calcitonin-related lins CRGP, junction; tight TJ, Abbreviations: level and the receptors. (CGRP) at PAR-2 targets: the particularly CALCRL of Pharmacological function, between activation RAMP-1, barrier place via the intestinal take MCs via the can the with TJs interact on MCs the MCs interaction the of The their and P). and neuron (substance inflammatory P afferent receptors of substance NK-1 the expression and between the CGRP interaction decreased of The and secretion cells kinase IL6. receptor mast as tropomyosin of that receptor, such degranulation neurotransmitters NGF markers prevented high-affinity and the K252a neuropeptides of via antagonist In of NGF recruitment Its release by leucotriens pain. activated A. the and are visceral to histamin, MCs sensitisation and leads sensitivity MCs. as activation, neurons the of increasing activate as (such activation thus the such MCs inflammation, direction neurons neurogenic the other membrane, the on by cell effects the mediators visceral numerous to and pro-inflammatory in nociceptors peristalsis bioactive results modulate of proteases) thus and secretion and signaling. bidirectionally The kinase intracellular communicate tyrosine of endings pain. protein nerve pro-inflammatory activation and The of and MCs transcription autophosphorylation notably. expression. through phosphorylation, degranulation of histamine process to cascade this vitro and a to production to participates cytokine leads Syk elements to This function and binding Fc individual. the factors, barrier receptor is sensitised activation intestinal high-affinity cells a its mast and on in for stimulus cell (IgE) classical E mast The immunoglobulins targets. of interactions, pharmacological and cell-nerve gut mast in on interactions bind of hand, illustration other opiates. Schematic system of the action nervous on slowing central antagonists, motor Peripheral into digestive 2: cross the entry Figure opioids. they thwarting of not tract since circle) action gastrointestinal do (blue action analgesic the opioids antagonists analgesic in the with mu-receptors central opioid mu-receptors antagonize treated the a not is peripheral on have Patient do whereas acting Opioids B) and by barrier, latter. circle). action the blood-brain (purple peripheral of antagonists the motricity a opioid the have inhibit peripheral also and and they tract barrier, digestive blood-brain the in the cross they since • • • • tde hwdta S 4 skihbtr lce usac ciainaddcesdcytokine decreased and activation P substance blocked inhibitor) (syk 143 GSK that showed studies niio ftepoentrsn iaeSk S 143 GSK Syk: kinase tyrosine protein the of Inhibitor K252a antagonist: NGF Capsaicin agonist: TRPV1 4096BS BIBN antagonist: CGRP α ,icuigurglto fedteilahso oeue uha ICAM1. as such molecules adhesion endothelial of upregulation including ), ε I ihant g receptor. IgE affinity high RI, 12 ε Icl ufc ro ocoslnigb allergen by cross-linking to prior surface cell RI α, IL1 β, IL6) In- Posted on Authorea 26 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162730098.86478422/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. niio fmcohg riietasotadnti xd rdcin(N-43 rvnsaueinflam- acute prevents (CNI-1493) Mass production Camb. An Med. oxide (1995). Mol. nitric al. lethality. et and endotoxin H., Schmidtmayerova, transport and G.A., mation arginine Zimmerman, macrophage M., Meistrell, of Liver O., Gastrointest. inhibitor Bloom, Physiol. P., peri- Ulrich, J. on M., Am. K252a Bianchi, ileus. antagonist postoperative factor rat growth for nerve implications of Physiol. degranulation: Effects cell (2015b). mast P. Vergara, toneal and cell J., Neurogastroenterol. mast Rychter, surgery. Soc. Peritoneal Berd´un, S., Motil. colorectal (2015a). 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F., inflammation Aihara, mucosal M., initiate Monya, M., macrophages Ushiki, N., Takahashi, K., Asano, function- PGs, REFERENCES lymphocyte oxide; LFA-1, nitric synthase; oxide NO, nitric transcription; inducible antigen-1. of iNOS, activator associated ; and 2 transducers cyclooxygenase kinase; Cox-2, signal N-terminal STATS, prostaglandin; c-Jun kB; JNK, factor LFA-1, protein; nuclear molecule-1; Mitogen-activated NF-kB, MAP, adhesion antigen-1; intercellular function-associated ICAM-1, 7 lymphocyte receptor-2; liposaccharide; proteinase-activated LPs, PAR2, receptor; receptor; toll-like choline TLR, junction; tight TJ, Abbreviations: targets: Pharmacological 7 of activation to • • • • 924–936. : tmlto fterlaeo ctlhln rmetrcnuos eetv H4aoit (mosapride agonists 5HT4 selective neurons: enteric from acetylcholine prucalopride). of and 3082 release ISIS the oligonucleotide of antisense Stimulation ICAM (CO) ICAM-1: Monoxide 2634 of Carbon CPSI Inhibition Kinase: Semapimod, MAP activation: of NF-kB Inhibitor and p38MAK of Inhibitor 309 6 7802. : G801-806. : α CRrcposta niisTFproduction. 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Wallace, undergoing trial in patients Laparoscopy in clinical (2011). strategy randomized al. perioperative a et best A.F., the surgery: is Engel, colonic management H.A., multimodal Cense, track D.T., fast Ubbink, with M.W., combination Hollmann, J., Wind, M.S., Vlug, 987–998. : 619–629. : 421–428. : 88 307 2692–2696. : G719-731. : 397 309 22 1139–1147. : 626–633. : 15 541–552. : 254 54 97 868–875. : 570–578. : 94–100. : 119 196 706–714. : 5130–5137. : 240 728–734; : 65 Posted on Authorea 26 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162730098.86478422/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. uci ta J al .docx 2 table BJP 531694-post-operative-ileus-a-pharmacological-perspective al et Buscail file Hosted 1.docx table BJP 531694-post-operative-ileus-a-pharmacological-perspective al calcitonin and et afferents Surg. Buscail spinal Ann. rats. of anesthetized Role in (1994). file ileus H.E. Hosted gastric Raybould, postoperative and the in V., peptide Plourde, gene-related Chem. S.N., Reddy, Med. J. T.T., disorders. Zittel, motility gastrointestinal of treatment the for vial at available vial at available 23 https://authorea.com/users/427522/articles/ https://authorea.com/users/427522/articles/ 37 2262–2265. : 219 79–87. : Posted on Authorea 26 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162730098.86478422/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. 24