Randomized, Double Blind, Pilot Study on the Effect of Intravenous Ibuprofen on Inflammatory Responses in Patients Undergoing Surgery With General Anesthesia: Correlation With Clinical Outcomes

This is a randomized, double-blind, placebo-controlled, two-arm parallel, multi-center study.

Thirty subjects (15 in each arm) will be enrolled. Subjects, over the age of 18, undergoing laparoscopic cholecystectomy under general anesthesia will be screened for eligibility to participate in the study. Subjects will be screened, recruited, and randomized during the preadmission visit or the day of surgery. Eligible subjects will be randomized to one of the two treatment group in a 1:1 ratio to receive either IV ibuprofen or matching placebo. Both men and women will be recruited, and there is no limitation as to racial and ethnic origin.

Participation in the study will not alter the patient's anesthetic management. Routine anesthesia monitors used during general anesthesia will be used. Patients will receive either 800mg IV ibuprofen or placebo pre-operatively. After pre-oxygenation, general anesthesia will be induced with lidocaine (1 mg/kg), propofol (1-2 mg/kg), and fentanyl (up to 5 mcg/kg). Tracheal intubation will be facilitated with rocuronium (0.6 mg/kg). Anesthesia will be maintained with air/oxygen (60%/40%), sevoflurane, and fentanyl. The anesthesiologist will be allowed to administer additional doses of fentanyl at his/her discretion. All patients will receive ondansetron 4 mg prior to the end of operation. Patients will be awakened and extubated in the OR and will be transferred to the Post Anesthesia Care Unit (PACU) after following simple commands. All patients will also be able to receive rescue doses of opioids as indicated by a Numeric Pain Rating Scale score >2 or upon request.

ii. Sample Size Justification: The proposed study is a pilot trial designed to explore the relationship between inflammatory markers and the quality of recovery. To our knowledge this vital connection has never been investigated. Therefore, we cannot use commonly accepted methods of sample size calculations. Mahdy et al examined levels of IL-6, IL-10, and cortisol in patients undergoing urological surgery and treated with indomethacin versus placebo (12). A sample size of twenty three patients per group was sufficient to show a difference in cytokine levels. Tasdogan et al compared levels of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-alpha in patients requiring postoperative ventilation after abdominal surgery and treated with dexmedetomidine versus propofol (18). A sample size of twenty patients per group was sufficient to demonstrate the difference in cytokine concentrations. Kim et al studied changes in cytokine levels in patients undergoing total abdominal hysterectomy and pretreated with clonidine (19). These investigators studied ten patients per group. The sample size was sufficient to demonstrate changes in IL-6 related to surgical stress. Therefore, we believe, that a sample size of 30 patients per group is an adequate sample to demonstrate the changes in level of inflammatory markers and explore the quality of recovery.

iii. IV ibuprofen administration The study drug will be given via intravenous infusion beginning after a placement of the IV line. The dose will be fixed at 800mg infused over 5 minutes.