The Median Effective Dose (ED50) of Paracetamol and Morphine : A Study of Interaction Study

Study Overview
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Brief Summary
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The aim of our study is to define the median effective analgesic doses (ED50) of paracetamol, morphine, and their combination and determination the nature of their interaction administered IV for postoperative pain after moderate painful surgery using up-and-down and isobolographic methods.

Detailed Description
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Ninety patients scheduled to undergo moderately painful surgery were included in one of three groups. Determination of median effective (ED50) doses was performed by the Dixon and Mood up-and-down method. Initial doses were 1.5g and 5mg, with dose adjustment intervals of 0.5g and 1 mg, in the paracetamol and morphine groups, respectively. The initial doses of paracetamol and morphine were 1.5g and 3mg, respectively in the paracetamol-morphine combination group with dose adjustment intervals of 0.25g for paracetamol and 0.5mg for morphine. Analgesic efficacy was defined as a decrease to less than 3 on a 0-10 numeric pain scale, 45 min after the beginning of drug administration. Isobolographic analysis was used to define the nature of their interaction.

Official Title
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The Median Effective Dose (ED50) of Paracetamol and Morphine for Postoperative Patients: A Study of Interaction.

Conditions
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Postoperative Pain

Intervention / Treatment
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* Drug: Paracetamol
* Drug: Morphine
* Drug: Paracetamol- Morphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASA physical status І or ІІ Moderately painful surgery patients postoperative pain more than 3 on a numerical pain score (NPS) - Exclusion Criteria: contraindication to the use of paracetamol and morphine Pregnancy age younger than 18 yr patient weight less 65kg intra-operative regional anesthesia, intra-operative administration of analgesics other than fentanyl, postoperative pain less than 3 on a numerical pain score (NPS)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paracetamol<br>initial doses was 1.5g g, with dose adjustment intervals of 0.5g . with maximum dose 2.5 g as an only starting dose / 24 h | Drug: Paracetamol<br>* initial doses was 1.5g, with dose adjustment intervals of 0.5g . with maximum dose 2.5 g as an only starting dose / 24 h<br>* Other names: Perfalgan;|
| Experimental: Morphine<br>Initial doses of morphine was 5mg, with dose adjustment intervals of 1 mg . | Drug: Morphine<br>* Initial of morphine was 5mg, with dose adjustment intervals 1 mg .<br>* Other names: Morphine sulfate;|
| Experimental: Paracetamol-morphine<br>The initial doses of paracetamol and morphine were 1.5g and 3mg, respectively in the paracetamol-morphine combination group with dose adjustment intervals of 0.25g for paracetamol and 0.5mg for morphine. | Drug: Paracetamol- Morphine<br>* The initial doses of paracetamol and morphine were 1.5g and 3mg, respectively in the paracetamol-morphine combination group with dose adjustment intervals of 0.25g for paracetamol and 0.5mg for morphine.<br>* Other names: Perfalgan-Morphine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ED50s of Paracetamol, morphine and their combination | the aim of our study is to define the median effective analgesic doses (ED50s) of paracetamol, morphine, and their combination to determine the nature of their interaction administered IV for postoperative moderately painful surgery using the Dixon and Mood up-and-down method and isobolographic analysis. | participants will be followed for the duration of hospital stay, an expected average of 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Paracetamol-Morphine interaction nature | the aim of our study is to define the median effective analgesic doses (ED50s) of paracetamol, morphine, and their combination to determine the nature of their interaction administered IV for postoperative moderately painful surgery using the Dixon and Mood up-and-down method and isobolographic analysis. | participants will be followed for the duration of hospital stay, an expected average of 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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paracetamol, morphine, median effective dose, pain