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October 12, 2014
8:00 AM - 10:00 AM
Room Hall B1-Area C
The Effect of Preoperative Administration of IV Ibuprofen on Stress Response in Patients Undergoing Laparoscopic Cholecystectomy
Vanny Le, M.D., Lakshmi N. Kurnutala, M.B.,B.S., Joel M. Yarmush, M.D., Joseph Schianodicola, M.D., Michael M. Haile, M.D., Lisa V. Doan, M.D., Catherine Schoenberg, B.S.N., C.R.C.C., Sergey Pisklakov, M.D., Alex Y. Bekker, M.D., Ph.D.
Rutgers - New Jersey Medical School, Newark, New Jersey, United States
Background: A stress response to surgery includes release of stress hormones (e.g. cortisol, catecholamines) and pro-inflammatory cytokines. This response is essential to tissue repair and wound healing. However, there has been emerging research suggesting that uncontrolled stress response may lead to a number of postoperative complications. We hypothesized that IV ibuprofen, a potent NSAID, may improve recovery characteristics of patients undergoing laparoscopic cholecystectomy by decreasing (modulating) inflammatory response.

Methods: 53 patients undergoing laparoscopic cholecystectomy were enrolled in this prospective, randomized, double-blinded study. Subjects received a single preoperative IV dose of ibuprofen 800 mg or placebo-saline. General anesthesia was induced with lidocaine, propofol, and fentanyl and maintained with air/oxygen, sevoflurane, and fentanyl. Blood samples were drawn before induction (preop), at the end of surgery (intraop), and in the PACU (postop) and analyzed for TNF-alpha, IL-1Beta, IL-2, IL-6, IL-10, IFN-gamma as well as cortisol, epinephrine, norepinephrine and CRP. Multiplexed bead-based immunoassays were used for analysis of cytokines, cortisol and CRP. Epinephrine and norepinephrine levels were determined by ELISA using Abnova Taiwan kits. Data were analyzed using a two-way repeated measure ANOVA to test for the effect of surgery and treatment group. Pairwise comparisons were assessed by t-test or rank test after correcting for multiple comparisons.

Results: Epinephrine and norepinephrine (Figure 1) increased in the intraop period in the placebo group and were significantly lower intraop for the Ibup group than the placebo group (epinephrine: placebo 0.23 ± 0.05 pg/mL vs. Ibup 0.11 ± 0.03 pg/mL, P = 0.004, norepinephrine: placebo 1.06 ± 0.12 pg/mL vs. Ibup 0.52 ± 0.09 pg/mL, P = 0.004).

Cortisol increased intraop and postop in both placebo and Ibup groups; however, cortisol levels were significantly lower postop for the Ibup group (173.6 ± 29.5 pg/mL vs.289.5 ± 25.9, P = 0.001). The CRP levels did not differ between treatment groups.

IFNγ, IL-1β and IL-2 cytokine concentrations were not detectable in many samples (Table 1). IL-10 values were significantly lower in the Ibup group postop (placebo 26.8 [0.1-113.0] pg/mL vs. Ibup 10.7 [0.1-32.2] pg/mL, P <0.001). There was an impact of drug treatment for TNFα intraop (placebo 11.1 [2.8-21.0] pg/mL vs. Ibup 18.7 pg/mL, P < 0.05) but no distinction between placebo and Ibup for IL-6.

Conclusion: Preoperative administration of IV Ibuprofen decreases catecholamines and cortisol postoperatively after laparoscopic cholecystectomy. Results show a variable impact of drug treatment on cytokines IL-10 and TNFα. Reduction in stress hormone concentrations may improve postoperative outcomes.
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