Synergistic Effect of Intravenous Ibuprofen and Hydromorphone for Postoperative Pain: Prospective Randomized Controlled Trial.

BACKGROUND An intravenous form of ibuprofen has recently been approved by the Food and Drug Administration (FDA) and reports are rare on its co-administration with opioids. OBJECTIVES We researched whether an intravenous ibuprofen-hydromorphone combination is synergistic, additive, or infra-additive on postoperative pain. STUDY DESIGN A parallel-group, 1:1:1 allocation, randomized, double-blind controlled trial. SETTING University teaching hospital in Korea. METHODS Ninety patients, undergoing breast surgery, were divided into one of the 3 groups (I, H, IH groups). Positive analgesic efficacy was defined as a numeric rating scale (NRS) 1.1), dose reduction index (DRI, a measure of how much the dose of each drug in a combination can be reduced), and isobologram were used to define the nature of their interaction. STATISTICS One way ANOVA, Kruskal Wallis test, and Chi square test, significance level P < 0.05. RESULTS The median effective doses (ED50) of ibuprofen and hydromorphone were 1,447 mg and 1.5 mg, respectively. The median ED50 of the combination was ibuprofen 71 mg and hydromorphone 0.3 mg. Ibuprofen and hydromorphone showed a strong synergy (CI 0.2, DRI 20 and 5 for ibuprofen and hydromorphone at ED50). LIMITATION Analgesic efficacy was observed during post-anesthesia care unit (PACU) period only. CONCLUSIONS The combination of intravenous ibuprofen and hydromorphone produces a strong synergistic analgesia on postoperative pain.