Administration of Acetazolamide to Prevent Remifentanil Induced Hyperalgesia

NCT02992938 | Completed Phase 4 DMC

• 1 other identifier: 803/16
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Hyperalgesia; Opioid-Related Disorders

Keywords

Opioid hyperalgesia; Acetazolamide; Remifentanil

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

  The first postoperative day

• Morphine consumption

  The first postoperative day

Study Arms (2)

Acetazolamide

EXPERIMENTAL

250 mg VO of acetazolamide will be administered the day of the surgery 2 hours before anesthesia induction

Drug: Acetazolamide

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

Drug: Placebo Oral Tablet

Interventions

Acetazolamide DRUG

Acetazolamide

Placebo Oral Tablet DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients scheduled for thyroidectomy with general anesthesia in the University of Chile Clinical Hospital

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Chile: lead

Study Sites (1)

Faculty of Medicine, University of Chile

Santiago, Santiago Metropolitan, 7563215, Chile

Location

Related Publications (4)

• 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.

  PMID: 23292683 RESULT

• 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.

  PMID: 21965050 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.

  PMID: 14581110 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.

  PMID: 15983467 RESULT

MeSH Terms

Conditions

Hyperalgesia; Opioid-Related Disorders

Interventions

Acetazolamide

Condition Hierarchy (Ancestors)

Somatosensory Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Rodrigo Gutierrez, MD

  Anesthesia Department, University of Chile

  PRINCIPAL INVESTIGATOR

• Antonello Penna, MD PhD

  Anesthesia Department, University of Chile

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 11, 2016
• First Posted: December 14, 2016
• Study Start: December 1, 2016
• Primary Completion: September 28, 2018
• Study Completion: September 28, 2018
• Last Updated: December 31, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

CL (1)