Administration of Acetazolamide to Prevent Remifentanil Induced Hyperalgesia

Study Overview
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Brief Summary
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Remifentanil is a potent opioid widely used during the administration of general anesthesia. There is a lot of evidence that suggest that the used of remifentanil is associated with the development of hyperalgesia (a reduction of nociceptive thresholds). However, the mechanism of this hyperalgesia is not fully understood. Recently, it was demonstrated that the disruption of the Cl- homeostasis could be involved. Interestingly, this was prevented in a murine model with the administration of Acetazolamide, a carbonic anhydrase inhibitor. In our clinical trial we will try to determine if the preoperative administration of acetazolamide could prevent the hyperalgesia induced by remifentanil in patients scheduled for thyroidectomy with general anesthesia.

Official Title
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Administration of Acetazolamide to Prevent Remifentanil Induced Hyperalgesia: Randomize Double Blind Clinical Trial

Conditions
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Hyperalgesia, Opioid-Related Disorders

Intervention / Treatment
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* Drug: Acetazolamide
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients scheduled for thyroidectomy with general anesthesia in the University of Chile Clinical Hospital Exclusion Criteria: Patients ASA III y IV Chronic pain history Drug and alcohol abuse Chronic use of opioid and sedatives Neuropsychiatric illness NSAID and other analgesics used the 48 hours previous to the surgery CMI > 30

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetazolamide<br>250 mg VO of acetazolamide will be administered the day of the surgery 2 hours before anesthesia induction | Drug: Acetazolamide<br> <br> |
| Placebo Comparator: Placebo<br>An oral tablet without active principle acetazolamide but with the same physical characteristics will be administered the day of the surgery 2 hours before anesthesia induction | Drug: Placebo Oral Tablet<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the mechanical pain threshold in an area distant to the site of the injury | The threshold will be determine using von Frey monofilaments before the surgery and will be compared 12-18 hours after the end of the surgery | 12-18 hours after the end of the surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the mechanical pain threshold in an area distant to the site of the injury |  | 2 hours after the end of the surgery | 
| Postoperative pain | A visual analogue scale (VAS; 0, no pain; 100, worst poss- ible pain) will be used to assess pain | The first postoperative day | 
| Morphine consumption | Morphine consumption with a patient controlled analgesia (PCA) in mg | The first postoperative day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opioid hyperalgesia, Acetazolamide, Remifentanil