Eunjung Oh1, Hyun Joo Ahn2, Woo Seog Sim, Jin Young Lee2. 1. Samsung Medical Centre, Sungkyunkwan University School of Medicine Seoul, Republic of Korea. 2. Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Korea.
Abstract
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)</= 3 on a 0 - 10 NRS, 30 minutes after the drug administration. Drugs were administered by the Dixon's up-and-down method. Starting doses were ibuprofen (I) 50 mg, hydromorphone (H) 0.25 mg, or ibuprofen 25 mg + hydromorphone 0.125 mg (IH). The maximum doses were ibuprofen 800 mg, hydromorphone 2 mg, or ibuprofen 400 mg + hydromorphone 1 mg. Combination index (CI) (additive: 0.9 - 1.1, synergism: < 0.9, antagonism: > 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.
RCT Entities:
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)</= 3 on a 0 - 10 NRS, 30 minutes after the drug administration. Drugs were administered by the Dixon's up-and-down method. Starting doses were ibuprofen (I) 50 mg, hydromorphone (H) 0.25 mg, or ibuprofen 25 mg + hydromorphone 0.125 mg (IH). The maximum doses were ibuprofen 800 mg, hydromorphone 2 mg, or ibuprofen 400 mg + hydromorphone 1 mg. Combination index (CI) (additive: 0.9 - 1.1, synergism: < 0.9, antagonism: > 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.
Authors: Kevin M Klifto; Ala Elhelali; Rachael M Payne; Carisa M Cooney; Michele A Manahan; Gedge D Rosson Journal: Cochrane Database Syst Rev Date: 2021-11-09
Authors: Roshni Rao; Rubie Sue Jackson; Barry Rosen; David Brenin; Wendy Cornett; Oluwadamilola M Fayanju; Steven L Chen; Negar Golesorkhi; Kandice Ludwig; Ayemoethu Ma; Starr Koslow Mautner; Michelle Sowden; Lee Wilke; Barbara Wexelman; Sarah Blair; Monique Gary; Stephen Grobmyer; E Shelley Hwang; Ted James; Nimmi S Kapoor; Jaime Lewis; Ingrid Lizarraga; Megan Miller; Heather Neuman; Shayna Showalter; Linda Smith; Joshua Froman Journal: Ann Surg Oncol Date: 2020-01-21 Impact factor: 5.344