RESUMO
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.
RESUMO
BACKGROUND: Epidural waveform analysis (EWA) provides a simple confirmatory adjunct for loss of resistance (LOR): when the needle/catheter tip is correctly positioned inside the epidural space, pressure measurement results in a pulsatile waveform. Epidural waveform analysis can be carried out through the tip of the needle (EWA-N) or the catheter (EWA-C). In this randomized trial, we compared the two methods. We hypothesized that, compared with EWA-C, EWA-N would result in a shorter performance time. METHODS: One hundred and twenty patients undergoing thoracic epidural blocks for thoracic or abdominal surgery were randomized to EWA-N or EWA-C. In the EWA-N group, LOR was confirmed by connecting the epidural needle to a pressure transducer. After obtaining a satisfactory waveform, the epidural catheter was advanced 5 cm beyond the needle tip. In the EWA-C group, the epidural catheter was first advanced 5 cm beyond the needle tip after the occurrence of LOR. Subsequently, the catheter was connected to the pressure transducer to detect the presence of waveforms. In both study groups, the block procedure was repeated at different intervertebral levels until positive waveforms could be obtained (through the needle or catheter as per the allocation) or until a predefined maximum of three intervertebral levels had been reached. Subsequently, the operator administered a 4 mL test dose of lidocaine 2% with epinephrine 5 µg/mL through the catheter. An investigator present during the performance of the block recorded the performance time (defined as the temporal interval between skin infiltration and local anesthetic administration through the epidural catheter). Fifteen minutes after the test dose, a blinded investigator assessed the patient for sensory block to ice. Success was defined as a bilateral block in at least two dermatomes. Furthermore, postoperative pain scores, local anesthetic consumption, and breakthrough analgesic consumption were recorded. RESULTS: No intergroup differences were found in terms of performance time, success rate, postoperative pain, local anesthetic requirement, and breakthrough analgesic consumption. CONCLUSION: EWA can be carried out through the needle or through the catheter with similar efficiency (performance time) and efficacy (success rate, postoperative analgesia). TRIAL REGISTRATION NUMBER: NCT03603574.