Nonsteroidal Anti-inflammatory Drugs and the Risk for Anastomotic Failure: A Report From Washington State’s Surgical Care and Outcomes Assessment Program (SCOAP) | Clinical Pharmacy and Pharmacology | JAMA Surgery | JAMA Network
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Schlachta  CM, Burpee  SE, Fernandez  C, Chan  B, Mamazza  J, Poulin  EC.  Optimizing Recovery After Laparoscopic Colon Surgery (ORAL-CS): effect of intravenous ketorolac on length of hospital stay.  Surg Endosc. 2007;2112):2212-2219.PubMedGoogle ScholarCrossref
Klein  M, Andersen  LPH, Harvald  T, Rosenberg  J, Gogenur  I.  Increased risk of anastomotic leakage with diclofenac treatment after laparoscopic colorectal surgery.  Dig Surg. 2009;26(1):27-30.PubMedGoogle ScholarCrossref
Holte  K, Andersen  J, Jakobsen  DH, Kehlet  H.  Cyclo-oxygenase 2 inhibitors and the risk of anastomotic leakage after fast-track colonic surgery.  Br J Surg. 2009;96(6):650-654.PubMedGoogle ScholarCrossref
Rushfeldt  CF, Sveinbjørnsson  B, Søreide  K, Vonen  B.  Risk of anastomotic leakage with use of NSAIDs after gastrointestinal surgery.  Int J Colorectal Dis. 2011;26(12):1501-1509.PubMedGoogle ScholarCrossref
Gorissen  KJ, Benning  D, Berghmans  T,  et al.  Risk of anastomotic leakage with non-steroidal anti-inflammatory drugs in colorectal surgery.  Br J Surg. 2012;99(5):721-727.PubMedGoogle ScholarCrossref
Charlson  ME, Pompei  P, Ales  KL, MacKenzie  CR.  A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.  J Chronic Dis. 1987;40(5):373-383.PubMedGoogle ScholarCrossref
Lee  TH, Marcantonio  ER, Mangione  CM,  et al.  Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery.  Circulation. 1999;100(10):1043-1049.PubMedGoogle ScholarCrossref
Silver  K, Desormaux  A, Freeman  LC, Lillich  JD.  Expression of pleiotrophin, an important regulator of cell migration, is inhibited in intestinal epithelial cells by treatment with non-steroidal anti-inflammatory drugs.  Growth Factors. 2012;30(4):258-266.PubMedGoogle ScholarCrossref
Freeman  LC, Narvaez  DF, McCoy  A,  et al.  Depolarization and decreased surface expression of K+ channels contribute to NSAID-inhibition of intestinal restitution.  Biochem Pharmacol. 2007;74(1):74-85.PubMedGoogle ScholarCrossref
Silver  K, Leloup  L, Freeman  LC, Wells  A, Lillich  JD.  Non-steroidal anti-inflammatory drugs inhibit calpain activity and membrane localization of calpain 2 protease.  Int J Biochem Cell Biol. 2010;42(12):2030-2036.PubMedGoogle ScholarCrossref
Simon  L, Mills  J.  Drug therapy: non-steroidal antiinflammatory drugs (first of two parts).  N Engl J Med. 1980;302(21):1179-1185.PubMedGoogle ScholarCrossref
Horan  TD, Noujaim  AA, McPherson  TA.  Effect of indomethacin on human neutrophil chemiluminescence and microbicidal activity.  Immunopharmacology. 1983;6(2):97-106.PubMedGoogle ScholarCrossref
Abramson  S, Edelson  H, Kaplan  H, Ludewig  R, Weissmann  G.  Inhibition of neutrophil activation by nonsteroidal anti-inflammatory drugs.  Am J Med. 1984;77(4B):3-6.PubMedGoogle ScholarCrossref
Stevens  DL.  Could nonsteroidal antiinflammatory drugs (NSAIDs) enhance the progression of bacterial infections to toxic shock syndrome?  Clin Infect Dis. 1995;21(4):977-980.PubMedGoogle ScholarCrossref
Busti  AJ, Hooper  JS, Amaya  CJ, Kazi  S.  Effects of perioperative antiinflammatory and immunomodulating therapy on surgical wound healing.  Pharmacotherapy. 2005;25(11):1566-1591.PubMedGoogle ScholarCrossref
Haws  MJ, Kucan  JO, Roth  AC, Suchy  H, Brown  RE.  The effects of chronic ketorolac tromethamine (toradol) on wound healing.  Ann Plast Surg. 1996;37(2):147-151.PubMedGoogle ScholarCrossref
Dong  YL, Fleming  RY, Yan  TZ, Herndon  DN, Waymack  JP.  Effect of ibuprofen on the inflammatory response to surgical wounds.  J Trauma. 1993;35(3):340-343.PubMedGoogle ScholarCrossref
Riley  GP, Cox  M, Harrall  RL, Clements  S, Hazleman  BL.  Inhibition of tendon cell proliferation and matrix glycosaminoglycan synthesis by non-steroidal anti-inflammatory drugs in vitro.  J Hand Surg Br. 2001;26(3):224-228.PubMedGoogle ScholarCrossref
Settipane  RA, Constantine  HP, Settipane  GA.  Aspirin intolerance and recurrent urticaria in normal adults and children: epidemiology and review.  Allergy. 1980;35(2:149-154.PubMedGoogle ScholarCrossref
Original Investigation
March 2015

Nonsteroidal Anti-inflammatory Drugs and the Risk for Anastomotic Failure: A Report From Washington State’s Surgical Care and Outcomes Assessment Program (SCOAP)

Author Affiliations
  • 1Department of Surgery, University of Washington Medical Center, Seattle
  • 2Department of Surgery, Madigan Army Medical Center, Ft Lewis, Washington
  • 3Department of Surgery, Swedish Medical Center, Seattle, Washington
  • 4Department of General and Vascular Surgery, Providence Medical Center, Everett, Washington
  • 5Department of Surgery, Virginia Mason Medical Center, Seattle, Washington
  • 6Department of Surgery, St Joseph Medical Center, Bellingham, Washington
  • 7Department of Surgery, Harborview Medical Center, Seattle, Washington
JAMA Surg. 2015;150(3):223-228. doi:10.1001/jamasurg.2014.2239

Importance  Nonsteroidal anti-inflammatory drugs (NSAIDs) have many physiologic effects and are being used more commonly to treat postoperative pain, but recent small studies have suggested that NSAIDs may impair anastomotic healing in the gastrointestinal tract.

Objective  To evaluate the relationship between postoperative NSAID administration and anastomotic complications.

Design, Setting, and Participants  Retrospective cohort study of 13 082 patients undergoing bariatric or colorectal surgery at 47 hospitals in Washington State from January 1, 2006, through December 31, 2010, using data from the Surgical Care and Outcomes Assessment Program linked to the Washington State Comprehensive Abstract Reporting System.

Exposure  NSAID administration beginning within 24 hours after surgery.

Main Outcomes and Measures  We used multivariate logistic regression modeling to assess the risk for anastomotic complications (reoperation, rescue stoma, revision of an anastomosis, and percutaneous drainage of an abscess) through 90 days after bariatric and colorectal surgery involving anastomoses.

Results  Of the 13 082 patients (mean [SD] age, 58.1 [15.8] years; 60.7% women), 3158 (24.1%) received NSAIDs. The overall 90-day rate of anastomotic leaks was 4.3% for all patients (151 patients [4.8%] in the NSAID group and 417 patients [4.2%] in the non-NSAID group; P = .16). After risk adjustment, NSAIDs were associated with a 24% increased risk for anastomotic leak (odds ratio, 1.24 [95% CI, 1.01-1.56]; P = .04). This association was isolated to nonelective colorectal surgery, for which the leak rate was 12.3% in the NSAID group and 8.3% in the non-NSAID group (odds ratio, 1.70 [95% CI, 1.11-2.68]; P = .01).

Conclusions and Relevance  Postoperative NSAIDs were associated with a significantly increased risk for anastomotic complications among patients undergoing nonelective colorectal resection. To determine the role of NSAIDs in colorectal surgery, future evaluations should consider specific formulations, the dose effect, mechanism, and other relevant outcome domains, including pain control, cardiac complications, and overall recovery.