Table 1.
Characteristics of included studies to determine the correlation between the use of NSAIDs and anastomotic leakage
| Author, year | Study design | Country, Institute | Recruitment period | Definition of AL | Diagnosis | Location of anastomosis | Urgency of surgery | N | NSAIDs administration | Quality assessmenta |
|---|---|---|---|---|---|---|---|---|---|---|
| Chen,18 2005 | RCT, Double‐blind | Taiwan, single | 2003 | NR | Mixed | Colorectal | Elective | 74 | PCA: ketolorac 1.2 g/mL + morphine 1 mg/mL 2 mL bolus and 10 min lockout until pain score <3 | 5 |
| Schlachta,19 2007 | RCT, Double‐blind | Canada, single | 2002‐2005 | NR | Mixed (Cancer 50%) | Colorectal | Elective | 44 | Ketolorac 30 mg IV every 6 h for 2 d after operation | 3 |
| Sim,20 2007 | RCT, Double‐blind | Singapore, single | 2002‐2004 | NR | Mixed (Cancer 94.9%) | Mixed (Colorectal 94.9%) | Elective | 79 | Valdecoxib 40 mg orally once pre‐operation and once daily for 5 d after operation | 2 |
| Xu,21 2008 | RCT, Double‐blind | China, single | 2006‐2007 | NR | Cancer | Colorectal | Elective | 40 | Flurbiprofen 1 mg/kg IV 30 min before and 6 h after skin incision | 5 |
| Chen,22 2009 | RCT, Double‐blind | Taiwan, single | 2006‐2007 | NR | Mixed | Colorectal | Elective | 102 | PCA: ketolorac 1.2 g/mL + morphine 1 mg/mL 2 mL bolus and 10 min lockout until pain score <3 | 4 |
| Wattchow,23 2009 | RCT, Double‐blind | Australia, 2 institutes | 2003‐2006 | NR | Mixed | Mixed (Colorectal 99%, Small intestine 1%) | Elective | 220 | Celecoxib 100 mg or Diclofenac 50 mg orally twice daily for 7 d or until discharge | 4 |
| Rosenberg,24 2007 | Retrospective cohort | Denmark, Single | 2004‐2006 | NR | Cancer | Colorectal | Elective | 310 | Diclofenac 75 mg twice daily, Not reported duration | 5 |
| Klein,26 2009 | Retrospective case‐control | Denmark, Single | 2004‐2007 | Leak requiring reoperation | Mixed (Cancer 96%) | Colorectal | Elective | 75 | Diclofenac 150 mg/d, Not reported duration | 7 |
| Holte,25 2009 | Retrospective cohort | Denmark, Single | 1997‐2006 | Radiologic finding or intra‐operative finding or clinical finding | NR | Colon | Elective | 502 | Ibuprofen 600 mg every 8 h or Celecoxib 200 mg every 12 h at POD 2‐8 | 7 |
| Gorissen,27 2012 | Retrospective cohort | Netherlands, 2 institutes | 2008‐2010 | Radiologic finding or intra‐operative finding or clinical finding | Mixed (Cancer 72%) | Colorectal | Mixed (Elective 86.4%) | 795 | NSAIDs use within POD 5 | 8 |
| Klein,28 2012 | Retrospective cohort | Denmark, 6 institutes | 2006‐2009 | Leak requring reoperation | Cancer | Colorectal | Elective | 2752 | NSAIDs use at least 2 d within POD 7 | 9 |
| Zittel,29 2013 | Retrospective cohort | Sweden, single | 2008‐2009 | NR | Mixed (Cancer 57.6%) | Colorectal | Elective | 205 | Etoricoxib 120 mg once daily, Not reported duration | 8 |
| Subendran,32 2014 | Retrospective case‐control | Canada, single | 2001‐2012 | Radiologic finding or intra‐operative finding | Mixed (IBD 65.6%, cancer 34.4%) | Colorectal | Elective | 262 | NSAIDs use within POD 5 | 8 |
| Saleh,31 2014 | Retrospective cohort | Canada, single | 2004‐2011 | Document at reoperation or Radiological finding | Mixed (Cancer 65.5%) | Colorectal | Elective | 731 | NSAIDs use within POD 5 | 8 |
| STARSurg UK,30 2014 | Prospective cohort | UK, multi‐institutes | 2013 | Radiologic finding or intra‐operative finding or clinical finding | Mixed (Cancer 62.1%) | Mixed (Colorectal 75.9%) | Mixed (Elective 72.1%) | 1503 | NSAIDs use within POD 2 | 8 |
| Paulsir,34 2015 | Retrospective cohort | USA, multi‐institutes | 2012‐2014 | Leaks requiring antibiotic or intervention or reoperation | NR | Colorectal | Mixed (Elective 78.6%) | 4360 | NSAIDs use within POD 1 | 9 |
| Hakkarainen,33 2015 | Retrospective cohort | USA, 47 institutes | 2006‐2010 | Leak requiring percutaneous drainage or reoperaion | NR | Bariatic, Colorectal | Mixed (Elective 87.6%) | 13082 | NSAIDs use within POD 1 | 9 |
| Raju,35 2015 | Retrospective cohort | Australia, 2 institutes | 2008‐2014 | Leak requiring percutaneous drainage or reoperaion | Mixed (Cancer 70.6%) | Colorectal | Elective | 267 | Celecoxib 100 mg twice daily start at 2 h before operation to POD 7 | 6 |
| Bakker,36 2016 | Retrospective cohort | Netherlands, single | 2006‐2013 | Leak requiring percutaneous drainage or reoperaion | Cancer | Colorectal | Elective | 856 | NSAIDs use at least 2 d until discharge | 8 |
| Rutegard,38 2016 | Retrospective cohort | Sweden, multi‐institutes | 2007‐2012 | Leak requiring percutaneous drainage or reoperaion | Cancer | Rectum | Elective | 2605 | NSAIDs use within POD 10 | 8 |
| Rushfeldt,37 2016 | Retrospective cohort with propensity score analysis | Norway, Single | 2007‐2009 | NR | Mixed (Cancer 52.8%) | Mixed (Colorectal 73.4%) | Mixed (Elective 88%) | 428 | NSAIDs use within POD 5 | 8 |
| Haddad,39 2017 | Retrospective cohort | USA, multi‐institutes | 2013‐2015 | NR | Trauma | Mixed (Small intestine 93.4%, Colorectal 6.6%) | Emergency | 533 | NSAIDs use 7 d prior to operation up to POD 14 | 7 |
| Fjederholt,41 2018 | Retrospective cohort | Denmark, 2 institutes | 2003‐2012 | Radiologic finding or endoscopic finding | Cancer | Esophagojejunostomy | Elective | 556 | NSAIDs use within POD 7 | 9 |
| Hultberg,40 2017 | Retrospective cohort | Sweden, 15 institutes | 2007‐2013 | Radiologic finding or intra‐operative finding or clinical finding or Endoscopic finding | Cancer | Rectal | Elective | 1495 | NSAIDs use at least 2 d within POD 7 | 9 |
Abbreviations: AL, anastomotic leakage; IBD, inflammatory bowel disease; NR, not reported; NSAIDs, non‐steroidal anti‐inflammatory drugs; PCA, patient controlled analgesia; POD, postoperative day; RCT, randomised controlled trial.
a
Quality assessment for RCT and observational studies using Jadad score and Newcastle‐Ottawa scale (NOS) for randomised controlled trials (RCTs) and observational studies, respectively.