Clinical trial NCT02992938: Administration of Acetazolamide to Prevent Remifentanil Induced Hyperalgesia
Official title: Administration of Acetazolamide to Prevent Remifentanil Induced Hyperalgesia: Randomize Double Blind Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hyperalgesia
Opioid-Related Disorders
Keywords: Opioid hyperalgesia
Acetazolamide
Remifentanil
Lead sponsor: University of Chile
Sponsor class: OTHER
First posted: 2016-12-14
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in the mechanical pain threshold in an area distant to the site of the injury
timeFrame: 12-18 hours after the end of the surgery
Secondary outcomes:
measure: Change in the mechanical pain threshold in an area distant to the site of the injury
timeFrame: 2 hours after the end of the surgery
measure: Postoperative pain
timeFrame: The first postoperative day
measure: Morphine consumption
timeFrame: The first postoperative day
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Faculty of Medicine, University of Chile
state: Metropolitana
Study officials:
affiliation: Anesthesia Department, University of Chile
name: Rodrigo Gutierrez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Anesthesia Department, University of Chile
name: Antonello Penna, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.