Comprehensive Analysis of the Effect of Ketorolac Administration after Pancreaticoduodenectomy

Abstract

Outcome improvement is a major goal of pancreatic surgery. Such efforts include decreasing perioperative narcotic use to optimize care and reduce potential contributions to the opioid crisis. Ketorolac, a frequent component of opioid-minimizing recovery pathways, has not been universally adopted over concerns regarding adverse events including anastomotic fidelity, hemorrhage, and renal failure. We examined ketorolac's effects on pancreatic fistula (PF) formation and related morbidity after pancreaticoduodenectomy (PD). A retrospective review of consecutive patients undergoing PD from December 2008 to September 2018 was conducted and stratified by receipt of ketorolac during the initial 5 postoperative days. The primary outcome was clinically relevant PF (CR-PF) per international consensus definitions. Secondary outcomes included fistula risk score (FRS)-adjusted CR-PF and cumulative morbidity. Of 429 patients, CR-PF occurred in 9.3% (n= 40), and 249 patients received ketorolac before postoperative day 6 (58.0%), with a mean dose of 36.1 ± 22.3 mg/day. CR-PF occurred in 11.2% (n= 28) of patients receiving ketorolac vs 6.7% (n= 12) who did not ( p= 0.12); CR-PF incidence was unrelated to dose. Overall CR-PF incidence did not differ statistically by ketorolac use in the first 5 days postoperatively across FRS categories. Results from multivariable logistic regression models, adjusted for known PF risk factors suggested that ketorolac was not significantly associated with risk of CR-PF (odds ratio [OR] 1.99 [range 0.93 to 4.26], p= 0.08). Operative mortality and major (Clavien ≥ 3) morbidity, including hemorrhage and renal failure, did not differ statistically between groups. Ketorolac administration was associated with an acceptable risk of CR-PF and no increase in major morbidity after PD. These data suggest ketorolac can be used in strategies to optimize analgesia and minimize opioid usage.