Synergistic Effect of Ibuprofen and Hydromorphone for Postoperative Pain

Study Overview
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Brief Summary
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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
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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.

Official Title
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Synergistic Effect of Ibuprofen and Hydromorphone for Postoperative Pain

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Ibuprofen
* Drug: Hydromorphone


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ibuprofen<br>Ibuprofen: Patients receive ibuprofen 50 mg, 100 mg, 200 mg, 400mg or 800 mg intravenously once at post-anesthesia care unit. | Drug: Ibuprofen<br>* Drug was administered by the Dixon and Mood up-and-down method. Starting doses was ibuprofen 50 mg. The maximum doses was ibuprofen 800 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.<br>* Other names: Caldolor;|
| Active Comparator: hydromorphone<br>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. | Drug: Hydromorphone<br>* Drug was administered by the Dixon and Mood up-and-down method. Starting doses was hydromorphone 0.25 mg. The maximum doses was hydromorphone 2 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.<br>* Other names: Dilid;|
| Active Comparator: ibuprofen+hydromorphone<br>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. | Drug: Ibuprofen<br>* Drug was administered by the Dixon and Mood up-and-down method. Starting doses was ibuprofen 50 mg. The maximum doses was ibuprofen 800 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.<br>* Other names: Caldolor;Drug: Hydromorphone<br>* Drug was administered by the Dixon and Mood up-and-down method. Starting doses was hydromorphone 0.25 mg. The maximum doses was hydromorphone 2 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.<br>* Other names: Dilid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain scores on the numeric rating scale (NRS) |  | postoperative 1 hour | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ibuprofen, hydromorphone, drug interactions