Ketorolac use may increase risk of postoperative pancreatic fistula after pancreaticoduodenectomy

Background Ketorolac (Toradol), a commonly used nonselective nonsteroidal anti-inflammatory drug (NSAID) in the postoperative period, has been associated with increased risk of anastomotic leak after colon resection. The effect of postoperative NSAID and ketorolac use on postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) is unknown. Methods Retrospective review of consecutive PDs at a high-volume pancreas center from 2012 to 2015. POPF was identified and graded using International Study Group on Pancreatic Fistula criteria. Demographics, operative variables and 30-d postoperative NSAID use, dosage, and timing (early = postoperative day [POD] 0-5, late > POD 5) were collected. Univariate and multivariate logistic regressions were used to identify predictors of POPF. Results Four hundred twenty-three PDs were analyzed (mean age 66 y, 47% female), and 60% received NSAIDs postoperatively. Ketorolac (median POD 0-5 cumulative dose = 90 mg, interquartile range 60-165) was used in 35.7% (n = 151). POPF occurred in 90 patients (21.3%). Early (POD 0-5) ketorolac use was associated with increased POPF, especially grade A (odds ratio [OR] 2.16, P = 0.036). Each 25 mg incremental increase in ketorolac use was associated with a 10% increase in the incidence of POPF (OR 1.10, P = 0.021), whereas a cumulative dose of >150 mg was associated with a 44% increased risk of POPF (OR 1.44, 95% confidence interval 1.03-2.01, P = 0.035). A multivariate regression model identified estimated blood loss, soft gland, pancreatic duct diameter, body mass index, and cumulative ketorolac dose >150 mg as independent predictors of POPF (P < 0.0001, pseudo R² = 0.149). Conclusions Increasing doses of ketorolac in the early postoperative period are associated with increased risk of POPF, whereas a cumulative dose of >150 mg is an independent predictor of POPF after PD.