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

ABSTRACT: 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.

SUBMITTER: Gutierrez R

PROVIDER: S-EPMC6842739 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Gutiérrez Rodrigo R Contreras Felipe F Blanch Alonso A Bravo Daniela D Egaña José I JI Rappoport Daniel D Cabané Patricio P Rodríguez Francisco F Penna Antonello A

Journal of pain research 20191106

<h4>Purpose</h4>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<sup>+</sup>-Cl<sup>-</sup> co-transporter KCC2, which was reverted using acetazolamide (ACTZ), a carbonic anhydrase inhibitor. We propose that ACTZ prevents remifentanil-mediated OIH in humans.<h4>Patients and methods</h4>We conducted a randomized, double-blind, ...[more]

PMID: 31807056

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Project description:BackgroundCough caused by endotracheal tube (ETT) placement is ubiquitous and correlates with adverse outcomes. Remifentanil administration via target-controlled infusion (TCI) is one of the cough prevention measures used during recovery. In a pilot study, lidocaine administered via the perforated outer cuff of a dual-cuff endotracheal tube was also found to prevent cough due to ETT placement. We therefore compared these two cough prevention approaches during recovery after thyroidectomy in a single-centre, double-blind, randomised study conducted in China during the period from 09/10/2020 to 30/04/2021.MethodsNinety-eight female patients aged 18-65 years with American Society of Anaesthesiologists Physical Status scores of I and II were scheduled to undergo thyroidectomy. The ETT contained an internal cuff covered by a perforated outer cuff to allow for lidocaine delivery. Patients were randomised to receive either 4 ml of saline solution (Group R, n = 49) or 4 ml of 2% lidocaine in the outer cuff (Group L, n = 49) at the beginning of skin suturing. Remifentanil (2 ng/ml) was maintained in Group R until extubation, while remifentanil was maintained in Group L until the end of skin suturing. The primary outcome was cough during patient transfer, at 1 min before extubation, and at extubation. The secondary outcomes were haemodynamics and other recovery parameters.ResultsPrimary outcomes were compared between remifentanil vs. lidocaine application, namely, the incidence of cough during patient transfer (0% in Group R vs. 0% in Group L), at 1 min before extubation (22.45% in Group R vs. 4.08% in Group L; P = 0.015), and at extubation (61.22% in Group R vs. 20.41% in Group L; P < 0.001). Compared with remifentanil, lidocaine more effectively decreased heart rate elevation and hypoxemia at 5 min after extubation, the spontaneous respiration recovery time, the extubation time, the duration of post-anaesthesia care unit (PACU) stay, Richmond Agitation-Sedation Scale scores in the agitated range and Critical-Care Pain Observation Tool scores.ConclusionLidocaine administered via the perforated outer cuff of the ETT significantly improved recovery from general anaesthesia compared to remifentanil in female patients after thyroidectomy.Trial registrationChinese Clinical Trial Registry (No. ChiCTR2000038653), registered on 27/09/2020.

Project description:BackgroundThe purpose of this study was to assess the effect of preoperative physiotherapy (PT) on functional, subjective and socio-economic parameters after total knee arthroplasty (TKA).Methods20 patients (mean ± SD: age 67 ± 7 years) scheduled for TKA at Balgrist University Hospital between July 2016 and March 2017 were randomly assigned to a control (CG) or intervention (IG) group. 3 to 4 weeks prior to surgery the IG completed 5 to 9 sessions of PT containing proprioceptive neuromuscular facilitation (PNF) techniques, endurance training and individually indicated interventions. Measurements were executed at baseline, preoperative and 3 months after TKA. The primary outcome measure was the Stair Climbing Test (SCT), secondary outcome measures were the knee range of motion (ROM) and the level of physical activity using Lysholm Score (LS) and Tegner Activity Scale (TAS). The subjective and socio-economic parameters were the Patients' Global Impression of Change (PGIC) scale, inpatient rehabilitation time, preoperative pain levels and metabolic equivalent (MET), postoperative intake of analgesics and overall costs.ResultsNo difference between IG and CG was found for SCT (F (2/36) = 0.016, p = 0.984, η2 = 0.004). An interaction between group and time was shown for TAS (F (18/1) = 13.890) with an increase in the IG (p = 0.002, η2 = 0.536). The sub-item "pain" within the LS presented a higher pain-level in CG (F (18/1) = 4.490, p = 0.048, η2 = 0.974), while IG showed a higher preoperative MET compared to CG (p = 0.035). There were no other significant changes. The CG produced 21.4% higher overall costs, took more analgesics and showed higher preoperative pain levels than the IG.ConclusionsFindings show that preoperative therapy improved the level of physical activity before and after TKA and resulted in a clinically relevant gain in TAS.Trial registrationClinicalTrials.gov Identifier; NCT03160534. Registered 19 May 2017.

Project description:BackgroundActivation of NMDA receptors play an important role in the development of remifentanil-induced hyperalgesia. We hypothesized that in addition to ketamine, intrathecal MgSO4 could also relieve thermal and mechanical hyperalgesia in rats.MethodsInitially, 24 Sprague-Dawley rats were divided into control group, remifentanil group, surgical incision group and remifentanil combined with surgical incision group to create an experimental model. Subsequently, 40 rats were divided into control group, model group, model group plus 100 ?g MgSO4, 300 ?g MgSO4 and 10 ?g ketamine respectively. Paw withdrawal mechanical thresholds and paw withdrawal thermal latency tests were performed at -24 h, 2 h, 6 h, 24 h, 48 h, 72 h and 7 day after the surgical procedure. After behavior assessment on the 7th day, remifentanil was given again to ascertain whether or not NMDA antagonists could suppress the re-exposure of remifentanil-induced hyperalgesia.ResultsRemifentanil administration plus surgical incision induced significant postoperative hyperalgesia, as indicated by decreased paw withdrawal mechanical thresholds and paw withdrawal thermal latency to mechanical and thermal stimulation. In addition to ketamine, intrathecal MgSO4 (100, 300 ?g) dose-dependently reduced remifentanil-induced mechanical and thermal hyperalgesia. Ketamine had less mechanical hyperalgesia in 6 h (p?=?0.018), 24 h (p?=?0.014) and 48 h (p?=?0.011) than 300 ?g MgSO4. There was no difference in inhibiting thermal hyperalgesia between the group ketamine and group MgSO4 (300 ?g). The rats were given remifentanil again 7 days later after the first exposure of remifentanil. The hyperalgesic effect induced by re-exposure of remifentanil was not reversed in any groups of MgSO4 or ketamine.ConclusionsIn addition to ketamine, intrathecal administration of MgSO4 dose-dependently reduced remifentanil-induced hyperalgesia in a surgical incision mode. Re-exposure to remifentanil 1 week later again produced hyperalgesia, and this was not altered by the prior intrathecal treatments in any 4 groups treated with MgSO4 or ketamine.

Dataset Information

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

Publications

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

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