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Safety and efficacy of non-steroidal anti-inflammatory drugs to reduce ileus after colorectal surgery

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Abstract Background Ileus is common after elective colorectal surgery, and is associated with increased adverse events and prolonged hospital stay. The aim was to assess the role of non-steroidal anti-inflammatory drugs (NSAIDs) for reducing ileus after surgery. Methods A prospective multicentre cohort study was delivered by an international, student- and trainee-led collaborative group. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The primary outcome was time to gastrointestinal recovery, measured using a composite measure of bowel function and tolerance to oral intake. The impact of NSAIDs was explored using Cox regression analyses, including the results of a centre-specific survey of compliance to enhanced recovery principles. Secondary safety outcomes included anastomotic leak rate and acute kidney injury. Results A total of 4164 patients were included, with a median age of 68 (i.q.r. 57–75) years (54·9 per cent men). Some 1153 (27·7 per cent) received NSAIDs on postoperative days 1–3, of whom 1061 (92·0 per cent) received non-selective cyclo-oxygenase inhibitors. After adjustment for baseline differences, the mean time to gastrointestinal recovery did not differ significantly between patients who received NSAIDs and those who did not (4·6 versus 4·8 days; hazard ratio 1·04, 95 per cent c.i. 0·96 to 1·12; P = 0·360). There were no significant differences in anastomotic leak rate (5·4 versus 4·6 per cent; P = 0·349) or acute kidney injury (14·3 versus 13·8 per cent; P = 0·666) between the groups. Significantly fewer patients receiving NSAIDs required strong opioid analgesia (35·3 versus 56·7 per cent; P < 0·001). Conclusion NSAIDs did not reduce the time for gastrointestinal recovery after colorectal surgery, but they were safe and associated with reduced postoperative opioid requirement.
Oxford University Press (OUP)
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Elliott J Bennett M Mcnamara S Sivarajah C Dunmore G Aitken M Nair M H Aly M Buari M M H Farhan-Alanie K Ahmed Z Sheikh M Monks J Lehmann O Rotimi T Bell D Limnatitou S Gormley P Taleongpong V Patel L Macgregor S Amini C Turner L Dwyer-Hemmings A Busuttil J Powell C Hensher F Vivian K Wcislo Z Millar S Hirosue I Ogunmwonyi D Nakakande I Kwek H Gaze A Nirmalanantha A M Bin Amran A Foulkes N Jones S Pillai G Khoury T Powell I Maleyko A Sangheli M Ransome M Isse O Aromolaran H Bholah J Anbarasan S Rehman E Hu S Timms W Reynolds A Hotchkies V Misra G Suresh V Murray L Theocharidou T Malik I Janmohamed B Carhart A Khan A Asif R Hullait P Quinn A Rylance S Butt J Leathes B J Finch T Philip Rajathasan H Jeddy H A Kyaw N Wong S Karelia J M Clements M Rainey N Joshi A Rahman M Gallagher N Rebuffa R Abdelgalil R Siaw Yen Lai N Laurence S Thomas C Green R Frostick R Khera M Povey H L Wong C McCusker L Hlukha G Pike F Kamel R Thakkar C Donaldson M Sequeira Campos Y Bhahirathan M N Armitage A S Hussain B Hardy M Y Hassan Serry J Herron M Bradbury T Osunronbi L Y C Tam A Khanan Kaabneh J Lawther P Fisher T Tribedi A Moosa A Ramdin M Goble E Downs L Wheldon E Baggus A Mandal A Nayeem S Ahmed W Fradley C Wilson S Gallagher T Criswell J Ward A Mukkavilli B Stubbs W Fordyce N Suchdev S Wei Lim Z Yi Tew S R Sookramanien A Chan G Bointas M Paul K L Ward M Bagnall S A Pherwani K Wang L Mitchell J Heyworth S Ayyar R Obukofe R Polson D Mason E Mackenzie C Russell N Doyle Z Habib M Zardab F Sartaj H Farooq M Tabibi D J Drury S J James R Barnett A B Teasdale E T J Richardson D A Thomas S Ahmed R L Williams H F Najabat-Lattif E Cahya G Lou M Coyle K Homyer L Y Zhu M Woods J Chang H O'Callaghan I Suchett-Kaye T H Mihailidis H Alawattegama E Seite A Barrett E Riordan W Lam M Dowdeswell C Mulvenna T Netke O Awokoya L Gurowich K Dhera S Hayat L Williams L Tincknell M Spazzapan F Teeling K Sysum J Latter M Latter S Khan M Guruswamy W Beedham E Brazier M Elghobashy M Bajaj H Mann E Etel M Woodmass H Hayden A Kisiel Y Ali S Husain A Arnold A C Pedersen P Cunha M Ahmed S Al Zawawi V Kudva F Y Liu K Theodoropoulou M Miscampbell A V Robinson J Johnston A Dharni S Lamb T Westerman E Evans L Campbell M Gillespie C M Cheong K Kulathevanayagam A Varghese S I Ike T S M Chu B Baljer J A W Mogg P Rai H A Claireaux M Williams R Smillie J Goetz E Appleby T Fadipe S Vaughan-Burleigh G Puri P Hussain P James R Flather A Cutler S Pathak J Sheldon T Collicott M al-Ausi A Mondal A Jovaisaite S M Shah N Khalid D Gutmann S Davison Y J Alame L Syed W J Owen S D Ahsan R Kalderon U Anthony-Uzoeto C Macleod Hall S Zheng K Wynter C James D Sapre R Ghosh J Baird L Cockburn O Blackwood H H Nadama W Simpson S Jeong S Bishop R Bate C Hobson A H Adam C Redclift J Do O Adeleye F Poli A Batterham S Brown J N Parekh W Clay K Pieri A Jackson S Brown A Saxena B Gurung T Oyebola F O'Brien B Djeugam S Gardezi S Ul-Hasan M P Martin-Hernandez M Sisley S Modi R Antakia A Elbayouk Y J Soh J Mather Z Yusuf Z Al-Sarraf M Naja S B Rassool J Convill Y Nikookam A Warsame J P H Tam C Pace M Kiandee R Ridwan C Carey F Hirri M J A McMillan J J Ling A Powell-Chandler L Pendelbury K Kerimzade A Tang E O Howard S Humayun O J Wadsworth K Tan F Abdelhameed C Haglund I Radnaeva N Hu S Rambhatla D Waldron P Madahar S Malik A Campbell L C Meney I Ibrahim C K Kang J Z J Chiu V Livie B Ibrahim M Khalil G Pooley B Shishkin R Gorgievska J Docherty A Southgate A Coomes F McGee S Flanagan C Thakrar Q J Tan H Anwar R Clough B Chrisp J Cassels G W V Cross A Ragavoodoo L Mercer C Mercer A Refalo R Hadley A McTighe F Farrow A Brodie G Davis D R Shah C Bowers S Patel O Morice A Burzic J Cheung A Shashidhara G Theodoraki J Birk A Ong M P E Ng R T W Wong S Maese B Yeap Z Iqbal D M Rojoa C Cabaleiro Barciela M Hussain C M Ruddy S Lindwe Y Qamar S Chuita T Melaugh J D Hall C Palmer O Kouli A S I Hassane A W Azhar T K Tan W Perchard T Scurr K Davidson E Campbell L Kelk A Ghosh A Gibbins D Mala A Loizidou O Hall L Mecia C Hew K Varathan L Tong B Chandrasekar L Giacci E Buchanan M O'Connell S Y Kwak E H Ong S Gardner J Lim C Maden M Illahi J Hale Z Xuan Tan S Edwards R Stahl J Stahl A Hickman D Collett Z Goolam-Mahomed B Allen A Atiyah H Ahmad J Jones O McGregor E Ogundiya F W Gan A Boulbadaoui O Kirnon-Jackman Q X Lim H Peckham T Yeoh S Q Yong J Y Chen S Siva Z H Sam M Gilani Y N Goh M G Muthukumar S Phillips R Makin-Taylor J Tjoakarfa A Giri S Suresan R Thavayogan C Y Hey P Thomas T A Johnson R I Williams A Rashid A Kushairi A Rais A James M Bugelli Y Chechelnitskaya N Sandhu C Toh R Tandon M Gray A Kumar C Ciurleo I Nyamali S Hiremath S Sinha M Chowdhary E Bradley M McTiernan S Macdonald S Sharkey N McLaughlin C Amey L Kraria O Skan C Kind J M Findlay P Tupper C Van Rhee S I Honeyman G Menon M Ahmed L Jegatheeswaran N Griffiths A Madhavan M Warne F L Malcolm T Lessware H T Wilkerson S Chatterjee-Woolman A Yoong W U R Ahmed A Longshaw O Flannery R Green M Leaning J Cragg H Sharriff C Doherty S Ganesananthan K W L Kwan L Sanders-Crook S Bhatia S Eames F Lewis P Kirupananthan Z Y Boh S Dass A Soma A Newton M Hill Y Shafiq M Brkljac L Boyce S Jasionowska W J English S Lam C Chipeta D Yilmaz C Jain T Garofalidou S A Novotny S Locke C Bowman A Begaj C Murphy K Radcliffe J T Chong M Poustie E Jeffrey N Chaudhury K Rajendran Z Akbar B Walters B Kulendrarajah N Tran S Shrestha S Parmar C Gallagher L Hennessy E Pentti S Badhrinarayanan A Fung M Mansoor R Kenny P Kan D E Lee S Khosla M Samake F Shaban R Aftab M Gough B Woodburn S Vayalapra K McMurrugh C Wong D Jimulia S Deol S Pike Y Embury-Young T Turner M Patel E Kilgallon R Keating A Walsh H Khan G Logue M Orekoya M Alasmar M Charalambides A Clavé Llavall E Williamson Y Bharwada S Zearmal H Evans M Panikkar G Cruz J Caplan A Ruparelia T Tanvir C Soare Y L Pang J Trotter A Zaidi V Thakrar P Pulickal H Ahmed J Parnell H Khan S Lennock V Ford W Pyc R Brignall D O'Neill R Hanna R Kane M Nicola K Rajput Y Xiao C Warner S Michael E 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Masiha J Tung B Shirazi A Neilson S Epton N Patel S Trussell A Couldrey C Donnelly S Eftychiou
Title: Safety and efficacy of non-steroidal anti-inflammatory drugs to reduce ileus after colorectal surgery
Description:
Abstract Background Ileus is common after elective colorectal surgery, and is associated with increased adverse events and prolonged hospital stay.
The aim was to assess the role of non-steroidal anti-inflammatory drugs (NSAIDs) for reducing ileus after surgery.
Methods A prospective multicentre cohort study was delivered by an international, student- and trainee-led collaborative group.
Adult patients undergoing elective colorectal resection between January and April 2018 were included.
The primary outcome was time to gastrointestinal recovery, measured using a composite measure of bowel function and tolerance to oral intake.
The impact of NSAIDs was explored using Cox regression analyses, including the results of a centre-specific survey of compliance to enhanced recovery principles.
Secondary safety outcomes included anastomotic leak rate and acute kidney injury.
Results A total of 4164 patients were included, with a median age of 68 (i.
q.
r.
57–75) years (54·9 per cent men).
Some 1153 (27·7 per cent) received NSAIDs on postoperative days 1–3, of whom 1061 (92·0 per cent) received non-selective cyclo-oxygenase inhibitors.
After adjustment for baseline differences, the mean time to gastrointestinal recovery did not differ significantly between patients who received NSAIDs and those who did not (4·6 versus 4·8 days; hazard ratio 1·04, 95 per cent c.
i.
0·96 to 1·12; P = 0·360).
There were no significant differences in anastomotic leak rate (5·4 versus 4·6 per cent; P = 0·349) or acute kidney injury (14·3 versus 13·8 per cent; P = 0·666) between the groups.
Significantly fewer patients receiving NSAIDs required strong opioid analgesia (35·3 versus 56·7 per cent; P < 0·001).
Conclusion NSAIDs did not reduce the time for gastrointestinal recovery after colorectal surgery, but they were safe and associated with reduced postoperative opioid requirement.

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