Synergistic Effect of Ibuprofen and Hydromorphone for Postoperative Pain

Not Applicable

Completed

• Conditions: Breast Cancer
• Interventions: Drug: Ibuprofen; Drug: Hydromorphone

• Registration Number: NCT02461056
• Lead Sponsor: Samsung Medical Center

Brief Summary

Intravenous form of ibuprofen is recently approved by FDA and reports are rare on the co-administration with opioids. The investigators searched whether intravenous ibuprofen-hydromorphone combination is synergistic, additive, or infra-additive on postoperative pain using combination index (CI), dose reduction index (DRI) and isobologram.

Detailed Description

Ninety patients, undergoing breast surgery, were included in one of the three groups (Ibuprofen, Hydromorphone, Ibuprofen+Hydromorphone groups). Positive analgesic efficacy was defined as a numeric rating scale (NRS) ≤3 on a 0-10 NRS, 30 min after the drug administration. Drug was administered by the Dixon and Mood up-and-down method. Starting doses were ibuprofen 50 mg, hydromorphone 0.25 mg, or ibuprofen 25 mg + hydromorphone 0.125 mg. 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.

Study Timeline

• Study Start: 2014-06
• Primary Completion: 2014-07
• Study Completion: 2014-07
• Status Verified: 2015-05
• Study First Submitted: 2015-05-28
• Study First Submitted QC: 2015-06-02
• Last Update Submitted: 2015-06-02
• Study First Posted: 2015-06-03
• Last Update Posted: 2015-06-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 90

Inclusion Criteria

• American Society of Anesthesiologists (ASA) physical status І or ІІ who were able to communicate and understand the pain scales

Exclusion Criteria

• any contraindication to the use of ibuprofen or hydromorphone
• a history of allergy or hypersensitivity
• a calculated creatinine clearance of <75 mL/min
• the presence or history of asthma, bleeding tendency, coronary artery bypass graft (CABG) surgery, heart failure, peptic ulcer disease, inflammatory bowel disease or any other gastrointestinal disorder, and renal or hepatic disease
• pregnancy
• age younger than 18 yr
• intraoperative use of regional anesthesia
• intraoperative administration of analgesics other than remifentanil
• postoperative pain ≤3 on a NRS in the post-anesthesia care unit (PACU)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ibuprofen+hydromorphone	Hydromorphone	Ibuprofen+Hydromorphone: Patients receive ibuprofen 25 mg + hydromorphone 0.125 mg, ibuprofen 50 mg + hydromorphone 0.25 mg, ibuprofen 100 mg + hydromorphone 0.5 mg, ibuprofen 200 mg + hydromorphone 0.75 mg, or ibuprofen 400 mg + hydromorphone 1 mg intravenously once at post-anesthesia care unit.
Ibuprofen	Ibuprofen	Ibuprofen: Patients receive ibuprofen 50 mg, 100 mg, 200 mg, 400mg or 800 mg intravenously once at post-anesthesia care unit.
hydromorphone	Hydromorphone	Hydromorphone: Patients receive hydromorphone 0.25 mg, 0.5 mg, 1 mg, 1.5 mg, or 2 mg intravenously once at post-anesthesia care unit.
ibuprofen+hydromorphone	Ibuprofen	Ibuprofen+Hydromorphone: Patients receive ibuprofen 25 mg + hydromorphone 0.125 mg, ibuprofen 50 mg + hydromorphone 0.25 mg, ibuprofen 100 mg + hydromorphone 0.5 mg, ibuprofen 200 mg + hydromorphone 0.75 mg, or ibuprofen 400 mg + hydromorphone 1 mg intravenously once at post-anesthesia care unit.

Primary Outcome Measures

Name	Time	Method
Pain scores on the numeric rating scale (NRS)	postoperative 1 hour

Trial Locations

Locations (1)

Samsung medical center; 🇰🇷 Seoul, Korea, Republic of