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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acetazolamide | Experimental | 250 mg VO of acetazolamide will be administered the day of the surgery 2 hours before anesthesia induction |
|
| Placebo | Placebo Comparator | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Acetazolamide | Drug |
| ||
| Placebo Oral Tablet |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rodrigo Gutierrez, MD | Anesthesia Department, University of Chile | Principal Investigator |
| Antonello Penna, MD PhD | Anesthesia Department, University of Chile | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Faculty of Medicine, University of Chile | Santiago | Santiago Metropolitan | 7563215 | Chile |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23292683 | Result | Ferrini F, Trang T, Mattioli TA, Laffray S, Del'Guidice T, Lorenzo LE, Castonguay A, Doyon N, Zhang W, Godin AG, Mohr D, Beggs S, Vandal K, Beaulieu JM, Cahill CM, Salter MW, De Koninck Y. Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl(-) homeostasis. Nat Neurosci. 2013 Feb;16(2):183-92. doi: 10.1038/nn.3295. Epub 2013 Jan 6. | |
| 21965050 |
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| ID | Term |
|---|---|
| D006930 | Hyperalgesia |
| D009293 | Opioid-Related Disorders |
| ID | Term |
|---|---|
| D020886 | Somatosensory Disorders |
| D012678 | Sensation Disorders |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000086 | Acetazolamide |
| ID | Term |
|---|---|
| D013830 | Thiadiazoles |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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|
| The first postoperative day |
| Morphine consumption | Morphine consumption with a patient controlled analgesia (PCA) in mg | The first postoperative day |
| Echevarria G, Elgueta F, Fierro C, Bugedo D, Faba G, Iniguez-Cuadra R, Munoz HR, Cortinez LI. Nitrous oxide (N(2)O) reduces postoperative opioid-induced hyperalgesia after remifentanil-propofol anaesthesia in humans. Br J Anaesth. 2011 Dec;107(6):959-65. doi: 10.1093/bja/aer323. Epub 2011 Sep 28. |
| 14581110 | Result | Angst MS, Koppert W, Pahl I, Clark DJ, Schmelz M. Short-term infusion of the mu-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal. Pain. 2003 Nov;106(1-2):49-57. doi: 10.1016/s0304-3959(03)00276-8. |
| 15983467 | Result | Joly V, Richebe P, Guignard B, Fletcher D, Maurette P, Sessler DI, Chauvin M. Remifentanil-induced postoperative hyperalgesia and its prevention with small-dose ketamine. Anesthesiology. 2005 Jul;103(1):147-55. doi: 10.1097/00000542-200507000-00022. |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000079524 | Narcotic-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
| D001393 |
| Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |