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Remifentanil-Induced Secondary Hyperalgesia Is Not Prevented By Preoperative Acetazolamide Administration In Patients Undergoing Total Thyroidectomy: A Randomized Controlled Trial

Authors Gutiérrez R, Contreras F, Blanch A, Bravo D, Egaña JI, Rappoport D, Cabané P, Rodríguez F, Penna A

Received 28 June 2019

Accepted for publication 17 September 2019

Published 6 November 2019 Volume 2019:12 Pages 2991—2997


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr E Alfonso Romero-Sandoval

Rodrigo Gutiérrez,1,2 Felipe Contreras,1 Alonso Blanch,1 Daniela Bravo,1 José I Egaña,1 Daniel Rappoport,3 Patricio Cabané,3 Francisco Rodríguez,3 Antonello Penna1,2

1Department of Anesthesiology and Perioperative Medicine, Hospital Clínico Universidad de Chile, Santiago, Chile; 2Centro de Investigación Clínica Avanzada (CICA), Facultad de Medicina and Hospital Clínico Universidad de Chile, Santiago, Chile; 3Head and Neck Surgery, Department of Surgery, Hospital Clínico Universidad de Chile, Santiago, Chile

Correspondence: Antonello Penna
Departmento de Anestesiología y Medicina Perioperatoria, Hospital Clínico, Universidad de Chile, Santos Dumont 999, Santiago 838 0456, Chile
Tel +56-2-29788209

Purpose: Acute administration of remifentanil may lead to opioid-induced hyperalgesia (OIH). Studies in mice suggest that OIH is mediated by impaired anionic homeostasis in spinal lamina I neurons due to a down-regulation of the K+-Cl co-transporter KCC2, which was reverted using acetazolamide (ACTZ), a carbonic anhydrase inhibitor. We propose that ACTZ prevents remifentanil-mediated OIH in humans.
Patients and methods: We conducted a randomized, double-blind, placebo-controlled clinical trial between December 2016 and September 2018. Patients were randomly allocated to receive ACTZ (250 mg of ACTZ 2 h before surgery) or placebo. To detect hyperalgesia, mechanical pain threshold (MPT) were measured before and after surgery using hand-held von Frey filaments in the forearm. Anesthesia was maintained with remifentanil at a target effect site of 4.5 ± 0.5 ng/mL, and sevoflurane at an end-tidal concentration of 0.8 MAC corrected for age.
Results: In total, 47 patients completed the study. Both groups were comparable in the baseline characteristics and intraoperative variables. Baseline MPT were similar in both groups. However, MPT in the forearm significantly diminished in the time in both groups. Finally, postoperative pain and morphine consumption were similar between groups.
Conclusion: Both groups developed remifentanil-mediated OIH at 12–18 h after surgery. However, ACTZ did not prevent the MPT reduction in patients undergoing total thyroidectomy.

Keywords: anesthesia, chloride dysregulation, carbonic anhydrase, pain

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