Opioid Induced Hyperalgesia (OIH) Modulation With Propranolol

Study Overview
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Brief Summary
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Opioid Induced Hyperalgesia (OIH) is an entity than has been demonstrated in healthy volunteers and in animal models. Is defined as an increase in the perception to painful stimuli, increasing the opioid requirements and diminishing the pain thresholds to stimuli. The apparition of OIH is also related to the exposure to opioids during surgery, depending of the dose, the time of exposition and the type of opioid. This condition can be modulated, specially in the perioperative context. It has been seen in healthy volunteers and in animal models, than the use of propranolol can modulate this phenomena, diminishing the postoperative requirements of analgesia. It is also unknown, the dose of propranolol required to modulate adequately OIH. The objective of this work is to evaluate the efficacy of propranolol in the modulation of opioid induced hyperalgesia, with lower postoperative requirements of analgesia rescue.

Detailed Description
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This is a randomized controlled study, comparing 2 interventions with a placebo. The interventions will be use of propranolol, at different doses, to achieve specific plasmatic concentrations. 80 patients will be required to find a difference of 20% in the primary outcome. The primary outcome to be measured is the postoperative use of opioids in the post anesthesic care unit. Secondary outcomes, will be the amount of opioids used in the following 24 hours to the surgery, the time to the first dose of analgesia in the post anesthesic care unit, and the change in the pain thresholds, evaluated as pain by pressure and by tactile sensitivity, before and after surgery. Also, as a secondary outcome, in a group than will not receive the study drug, we will evaluate the temporal changes in opioid induced hyperalgesia, by pain sensitivity measured in the postoperative hours 2, 4 and 24. 10 patients receiving placebo will be part of this additional measures.

Official Title
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Opioid Induced Hyperalgesia (OIH) Modulation With Propranolol, in Laparoscopic Abdominal Surgery

Conditions
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Hyperalgesia

Intervention / Treatment
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* Drug: Propranolol
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients scheduled for elective laparoscopic cholecystectomy American Society of Anesthesiology Score (ASA) I-II Exclusion Criteria: Medical history of cardiac disease Medical history of respiratory disease Regular use of beta blockers Known allergies to drugs used in the study Known history of illicit drugs use

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Saline solution by target controlled infusion | Drug: Saline<br>* Saline as placebo<br>* Other names: Placebo;|
| Active Comparator: Propranolol at 5ng/ml target dose<br>Propranolol iv by target controlled infusion, to achieve a plasmatic concentration of 5ng/ml | Drug: Propranolol<br>* propranolol iv by target controlled infusion, to achieve specific plasmatic concentration goals<br>* Other names: Beta blocker;|
| Active Comparator: Propranolol at 15ng/ml target dose<br>Propranolol iv by target controlled infusion, to achieve a plasmatic concentration of 15ng/ml | Drug: Propranolol<br>* propranolol iv by target controlled infusion, to achieve specific plasmatic concentration goals<br>* Other names: Beta blocker;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative opioid use | Dose of opioid required to manage pain adequately | 24 hours posterior to surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain thresholds (heat) | Evaluation of the threshold to perceive a heat perception as pain | 24 hours posterior to surgery | 
| Pain thresholds (cold) | Evaluation of the threshold to perceive a cold perception as pain | 24 hours posterior to surgery | 
| Pain thresholds (tactile sensitivity) | Evaluation of pain by tactile sensitivity, using the PinPrick system | 24 hours posterior to surgery | 
| Temporal changes in pain sensibility | Evaluation of pain by tactile sensitivity, using the PinPrick system | 24 hours posterior to surgery |