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Objectives: Our purpose was to explore the effect of remifentanil on acute and chronic postsurgical pain after cardiac surgery., Materials and Methods: Randomized controlled trials were retrieved from electronic databases, such as PubMed, Cochrane Library, China National Knowledge Internet databases, Scopus, and Web of Science. A systematic review, meta-analysis, and trial sequential analysis (TSA) were performed. Basic information and outcomes were extracted from the included studies. The primary outcome was chronic postsurgical pain. Secondary outcomes were scores of postsurgical pain and morphine consumption within 24 hours after cardiac surgery. Risk of bias (ROB) assessment was based on the Cochrane ROB tool version 2. The overall quality of the evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system., Results: Seven studies consisting of 658 patients were enrolled in the meta-analysis. A single study had a high ROB and 2 studies had a moderate ROB. The incidence of chronic postsurgical pain (4 studies [415 patients]; risk ratio: 1.02 [95% CI: 0.53 to 1.95]; P = 0.95; I2 = 59%; TSA-adjusted CI: 0.78 to 1.20) and the postsurgical pain score (2 studies [196 patients]; mean difference: 0.09 [95% CI: -0.36 to 0.55]; P = 0.69; I2 = 0%; TSA-adjusted CI: -0.36 to 0.55) were not statistically different between the 2 groups. However, morphine consumption (6 studies [569 patients]; mean difference: 6.94 [95% CI: 3.65 to 10.22]; P < 0.01; I2 = 0%; TSA-adjusted CI: 0.00 to 0.49) was higher in the remifentanil group than in the control group., Conclusion: There was not enough evidence to prove that remifentanil can increase the incidence of chronic postsurgical pain after cardiac surgery, but interestingly, the results tended to support a trend toward increased complications in the intervention group. However, there was moderate certainty evidence that the use of remifentanil increases the consumption of morphine for analgesia, and more direct comparison trials are needed to inform clinical decision-making with greater confidence., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This meta-analysis aimed to explore the correlation between the different doses of remifentanil-based anaesthesia and postoperative pain in randomised trials., Methods: The electronic databases including PubMed, Cochrane, clinical trial registries, and Google Scholar were searched up to November 2022 for randomised controlled trials (RCTs) that assessed the dose dependent efficacy of remifentanil for postoperative pain intensity and hyperalgesia., Results: 31 studies involving 2019 patients were included for analysis. Compared with the high remifentanil dose administration, patients in low doses showed less postoperative pain intensity at 1-2 h (weighted mean differences (WMD): 0.60, 95% CI, 0.05 to 1.15), 3-8 h (WMD: 0.38, 95% CI, 0.00 to 0.75), 24 h (WMD: 0.26, 95% CI, 0.04 to 0.48) and 48 h (WMD: 0.32, 95% CI, 0.09 to 0.55). Remifentanil-free regimen failed to decrease the pain score at 24 h (WMD: 0.10, 95% CI, -0.10 to 0.30) and 48 h (WMD: 0.15, 95% CI, -0.22 to 0.52) in comparison with remifentanil-based anaesthesia. After excluding trials with high heterogeneity, the dose of the remifentanil regimen was closely correlated with the postoperative pain score (P=0.03). In addition, the dose of the remifentanil regimen was not associated with the incidence of postoperative nausea and vomiting (PONV) (P=0.37)., Conclusions: Our meta-analysis reveals that the low dose of remifentanil infusion is recommendable for general anaesthesia maintenance. No evidence suggests that remifentanil-free regimen has superiority in reducing postoperative pain. Moreover, remifentanil doesn't have a dose dependent effect in initiating PONV., Trial Registration: The protocol of present study was registered with PROSPERO (CRD42022378360)., (© 2024. The Author(s).)

Remifentanil-induced hyperalgesia (RIH) is a severe but common postoperative clinical problem with elusive underlying neural mechanisms. Here, we discovered that glutamatergic neurons in the thalamic ventral posterolateral nucleus (VPLGlu) exhibited significantly elevated burst firing accompanied by upregulation of Cav3.1 T-type calcium channel expression and function in RIH model mice. In addition, we identified a glutamatergic neuronal thalamocortical circuit in the VPL projecting to hindlimb primary somatosensory cortex glutamatergic neurons (S1HLGlu) that mediated RIH. In vivo calcium imaging and multi-tetrode recordings revealed heightened S1HLGlu neuronal activity during RIH. Moreover, preoperative suppression of Cav3.1-dependent burst firing in VPLGlu neurons or chemogenetic inhibition of VPLGlu neuronal terminals in the S1HL abolished the increased S1HLGlu neuronal excitability while alleviating RIH. Our findings suggest that remifentanil induces postoperative hyperalgesia by upregulating T-type calcium channel-dependent burst firing in VPLGlu neurons to activate S1HLGlu neurons, thus revealing an ion channel-mediated neural circuit basis for RIH that can guide analgesic development.

Objective: To explore the changes of entropy index and cerebral oxygen metabolism in the maintenance of remifentanil anesthesia and the predictive value of postoperative hyperalgesia., Methods: A total of 266 patients undergoing general anesthesia in our hospital from January 2020 to October 2021 were selected, and remifentanil was used to maintain anesthesia. The state entropy, reaction entropy, and cerebral oxygen metabolism indexes (cerebral oxygen uptake rate (CERO 2 ), arterial-venous blood oxygen difference (Da-jvO 2 )) of patients before induction of anesthesia, 15 minutes during the operation, and at the end of the operation were compared. The influencing factors of postoperative hyperalgesia were analyzed. The logistic regression model of postoperative hyperalgesia was established, and the value of entropy index and cerebral oxygen metabolism in predicting postoperative hyperalgesia was evaluated by drawing the receiver operating characteristic curve (ROC)., Results: The state entropy, response entropy, and CERO 2 at 30 min during the operation and at the end of the operation were lower than those before the induction of anesthesia, and Da-jvO 2 was higher than that before the induction of anesthesia ( P < 0.001). At the end of the operation, the state entropy, reaction entropy, and CERO 2 were higher than 30 minutes during the operation, and Da-jvO 2 was lower than 30 minutes during the operation ( P < 0.001). The dosage of remifentanil, reaction entropy, and CERO 2 at the end of the operation entered the logistic model. The AUC value of the reaction entropy and CERO 2 combined to predict postoperative hyperalgesia at the end of the operation was 0.851 greater than the reaction entropy at the end of the operation ( χ 2 = 3.847, P = 0.036), CERO 2 ( χ 2 = 2.589, P = 0.010) single index predictive value., Conclusion: The entropy index and cerebral oxygen metabolism in general anesthesia patients change with the progress and discontinuation of remifentanil maintenance anesthesia, and the combination of the two has a high predictive power in postoperative hyperalgesia risk assessment. When the reaction entropy > 54.23, CERO 2 > 34.14%, or the total dosage of remifentanil ≥ 30  μ g/kg at the end of the operation, we should be highly vigilant of the occurrence of postoperative hyperalgesia and postoperative analgesia management should be strengthened., Competing Interests: The authors declare no competing interests., (Copyright © 2022 Tianhao Zhang and Fang Ma.)

Background: Adolescent idiopathic scoliosis (AIS) surgery is associated with significant postoperative pain. Remifentanil is a short-acting opioid that is often used as a component of total intravenous anesthesia. Remifentanil has been implicated in acute opioid tolerance and opioid-induced hyperalgesia, resulting in increased postoperative pain and opioid consumption. This retrospective study sought to investigate the relationship between the dose of intraoperative remifentanil and cumulative postoperative opioid consumption through 72 hours following surgery for pediatric AIS patients., Methods: We performed a retrospective chart review of adolescent patients undergoing posterior spine instrumentation under total intravenous general anesthesia at a single major pediatric center between January 2015 and October 2017. The relationship between intraoperative cumulative weight-adjusted remifentanil dose and logarithmic transformation of cumulative weight-adjusted opioid consumption through 72 hours following surgery was examined by regression analysis. A priori determined potential confounding variables were collected, including demographic data, perioperative analgesic agents (ie, ketamine, dexmedetomidine, and acetaminophen), surgical duration, vertebrae instrumented, and blood transfusion. Multivariable linear regression analysis was used to adjust for these possible confounding variables., Results: Eighty-nine patients met inclusion criteria, of which 78 had complete data for analysis. Univariable linear regression analysis revealed no association between remifentanil dose and opioid consumption through 72 hours following surgery (slope = 0.79 [95% confidence interval [CI], 0.61-0.98; R2 = 0.0039; P = .588]). After adjustment for possible confounding factors, no relationship between remifentanil dose (regression coefficient (coeff.) -0.08; 95% CI, -1.59 to 1.43; P = .912) and opioid consumption through 72 hours was found (slope =0.90 [95% CI, -0.65 to 2.46]; R2 = 0.1634). Similar results were obtained when the model was repeated for opioid consumption in postanesthesia care unit (PACU)., Conclusions: In this study examining adolescent patients undergoing surgery for idiopathic scoliosis, no association was found between the dose of intraoperative remifentanil and postoperative opioid consumption in the context of a propofol-based total intravenous anesthetic and multimodal analgesia. These results provide direction for future prospective controlled studies to further evaluate this relationship., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

This study measured the number of complications after deep inferior epigastric perforator (DIEP) flap reconstruction performed under opioid-free anesthesia (OFA) combined with goal-directed fluid therapy or opioid anesthesia with liberal fluid therapy (OA). This retrospective cohort study consisted of 204 patients who underwent DIEP flap reconstruction at AZSint Jan Brugge between April 2014 and March 2019. Primary outcomes were complications, according to the Clavien-Dindo classification and the length of hospital stay (LOS). The secondary outcomes were flap failure, postoperative nausea and vomiting (PONV), postoperative pain, postoperative opioid consumption, and postoperative skin flap temperature. OFA included a combination of dexmedetomidine, lidocaine, and ketamine without any opioid administered pre- or intraoperatively. OA included a combination of sufentanil and remifentanil. OFA patients received strict goal-directed fluid therapy, whereas OA patients received liberal fluids to maintain perfusion pressure. All patients except 7 (TIVA with remifentanil) received inhalation anesthesia combined with an infusion of propofol. Of the 204 patients, 55 received OFA and 149 received OA. There were no differences in major complications, but fewer minor complications in the OFA group (17.9% vs. 51.4% and P < 0.001). Flap failure occurred in three patients of the OA group. Six patients developed flap thrombosis (five OA patients and one OFA patient). OFA was associated with fewer postoperative opioids, shorter LOS, less PONV, and less pain. In patients without previous nausea, the PONV incidence was higher in the OA group than in the OFA group (12.7% vs. 43.6% and P < 0.001). Patients with previous nausea more frequently required postoperative opioids and had a nausea rate of 60.87%., Competing Interests: Declaration of Competing Interest Harold Mulier: None. Bob De Frene: None. Lara Benmeridja: None. Florian Vanhoorebeeck: None. Bruno Denis: None. Bob Casaer: None. Fabrice Rogge: None. Kris Leleu: None. Jan Mulier: Personal fees, department grants, financial, and nonfinancial support to organize scientific meetings from MSD Merck, GE Healthcare, and Johnson & Johnson outside the submitted work., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: This RCT investigated the effect of opioid titration by three different nociception monitoring devices or clinical signs during general anaesthesia., Methods: Ninety-six patients undergoing radical retropubic prostatectomy with propofol/remifentanil anaesthesia were randomised into one of four groups to receive remifentanil guided by one of three nociception monitoring devices (surgical pleth index [SPI], pupillary pain index [PPI], or nociception level [NOL]) or by clinical judgement (control). Intraoperative remifentanil requirement was the primary endpoint, whereas recovery parameters and stress hormone levels were secondary endpoints., Results: The mean [95% confidence interval {CI}] remifentanil administration rate differed between the groups: control 0.34 (0.32-0.37), SPI 0.46 (0.38-0.55), PPI 0.07 (0.06-0.08), and NOL 0.16 (0.12-0.21) μg kg -1 min -1 (P<0.001). Intraoperative cessation of remifentanil administration occurred in different numbers (%) of patients: control 0 (0%), SPI 1 (4.3%), PPI 18 (75.0%), and NOL 11 (47.8%); P=0.002. The area under the curve analyses indicated differences in cumulative cortisol levels (mg L -1 min -1 ) amongst the groups: control 37.9 (33.3-43.1), SPI 38.6 (33.8-44.2), PPI 72.1 (63.1-82.3), and NOL 54.4 (47.6-62.1) (mean [95% CI]). Pairwise group comparison results were as follows: control vs SPI, P=0.830; control vs PPI, P<0.001; control vs NOL, P=0.001; SPI vs PPI, P<0.001; SPI vs NOL, P=0.002; and PPI vs NOL, P=0.009., Conclusions: The nociception monitoring devices and clinical signs reflect the extent of nociception differently, leading to dissimilar doses of remifentanil. Very low remifentanil doses were associated with an increase and higher remifentanil doses were accompanied by a decrease in serum cortisol concentrations. Use of nociception monitoring devices for guiding intra-operative opioid dosing needs further validation., Clinical Trial Registration: NCT03380949., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Consecutive exposure to high-dose remifentanil during anesthesia may induce remifentanil-induced postinfusion hyperalgesia (RPH). Dexmedetomidine, a highly selective α2-adrenergic receptor agonist, may have synergistic effects with opioids and aid in perioperative pain management. In this study, we hypothesized that an intraoperative bolus dose of intravenous dexmedetomidine could alleviate RPH in patients undergoing thyroidectomy under general anesthesia., Methods: Ninety patients undergoing thyroidectomy were randomly assigned to 1 of 3 groups: placebo, normal saline (group P); low-dose dexmedetomidine 0.2 μg·kg-1 (group LD); or high-dose dexmedetomidine 0.5 μg·kg-1 (group HD). Remifentanil was infused at a rate of 0.30 μg·kg-1·minute-1. Mechanical pain thresholds were measured using an Electronic von Frey device preoperatively and at 30 minutes, 6 hours, 24 hours, and 48 hours after surgery and were analyzed with 2-way repeated-measures analysis of variance (ANOVA) followed by Bonferroni post hoc comparison. We also recorded postoperative pain scores, the incidence of receiving rescue analgesics, and side effects up to 48 hours after surgery., Results: The mechanical pain thresholds around the skin incision were significantly higher in group LD compared to group P 30 minutes and 6 hours after surgery (mean ± standard deviation: [65.0 ± 25.2] vs [49.6 ± 24.4] g, mean difference [95% confidence interval]: 15.4 [0.3-30.5] g, P = .045 at 30 minutes; [65.9 ± 24.5] vs [49.3 ± 26.1] g, 16.6 [1.1-32.1] g, P = .032 at 6 hours). The pain thresholds around the skin incision were significantly higher in group HD compared to group P 30 minutes and 6 hours after surgery ([67.8 ± 21.7] vs [49.6 ± 24.4] g, 18.2 [3.1-33.3] g, P = .013 at 30 minutes; [68.3 ± 22.5] vs [49.3 ± 26.1] g, 19.0 [3.5-34.5] g, P = .011 at 6 hours). The incidence of hyperalgesia around the skin incision was lower in group HD than in group P 30 minutes and 6 hours after surgery (4 [13%] vs 14 [48%], P = .012 at 30 minutes, 4 [13%] vs 12 [41%], P = .045 at 6 hours), although no significant difference was observed between group LD and group P. Postoperative pain scores, the incidence of rescue analgesic demand, and postoperative side effects were not significantly different between the groups., Conclusions: An intraoperative intravenous bolus dose of dexmedetomidine 0.5 μg·kg-1 alleviates remifentanil-induced hyperalgesia in patients undergoing thyroidectomy without a significant difference in side effects., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 International Anesthesia Research Society.)

Aim: Investigate the potential role of OPRM1 (mu-opioid receptor) and COMT (catechol-O-methyltransferase enzyme) polymorphisms in postoperative acute, chronic and experimental thermal pain. Methods: A secondary analysis of 125 adult cardiac surgery patients that were randomized between fentanyl and remifentanil during surgery and genotyped. Results: Patients in the fentanyl group with the COMT high-pain sensitivity haplotype required less postoperative morphine compared with the average-pain sensitivity haplotype (19.4 [16.5; 23.0] vs 34.6 [26.2; 41.4]; p = 0.00768), but not to the low-pain sensitivity group (30.1 [19.1; 37.7]; p = 0.13). No association was found between COMT haplotype and other pain outcomes or OPRM1 polymorphisms and the different pain modalities. Conclusion: COMT haplotype appears to explain part of the variability in acute postoperative pain in adult cardiac surgery patients.

Background: Postoperative pain represents an important concern when remifentanil is used for total intravenous anesthesia because of its ultrashort half-life. Longer acting opioids, such as sufentanil, have been used during induction of remifentanil-based total intravenous anesthesia as a means to overcome this shortcoming. However, the effectiveness and safety of such strategy still lacks evidence from randomized clinical trials. Hence, we aimed to assess the postoperative analgesic efficacy and safety of a single dose of sufentanil administered during the induction of remifentanil-based total intravenous anesthesia., Methods: Forty patients, scheduled for elective open abdominal surgery, were randomized to receive remifentanil-based total intravenous anesthesia with or without a single dose of sufentanil upon induction. We assessed the postoperative morphine consumption administered through a patient-controlled analgesia pump. Self-reported pain scores and the occurrence of nausea, vomiting, pruritus, agitation, somnolence and respiratory depression were also assessed up to 2 days after surgery., Results: The mean difference between the sufentanil and control groups regarding morphine consumption in the post-anesthetic care unit and at 12, 24 and 48h after surgery were -7.2mg (95%CI: -12.5 to -2.1, p<0.001), -3.9mg (95%CI: -11.9 to 4.7, p=0.26), -0.6mg (95%CI: (-12.7 to 12.7, p=0.80), and -1.8mg (95%CI: (-11.6 to 15.6, p=0.94), respectively. Neither self-reported pain nor the incidence of adverse events were significantly different between groups at any time point., Conclusion: Our findings suggest that the administration of sufentanil during induction of remifentanil-based total intravenous anesthesia is associated with decreased early postoperative opioid consumption., (Copyright © 2019 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.)

Background: Mismanagement of remifentanil leads to severe side effects such as opioid-induced tolerance and hyperalgesia. Recently studies revealed an alternative withdrawal method to limit these side effects. A gradual withdrawal of remifentanil seems to be associated with less pain. The hypothesis of this double-blinded, randomized controlled trial was that a gradual withdrawal of remifentanil would be associated with less immediate post-operative pain compared to after an abrupt discontinuation of remifentanil in patients who underwent thyroid surgery., Methods: This double-blinded, randomized controlled trial was conducted in a tertiary level hospital in Brussels (Belgium) from April until August 2017. 34 patients undergoing thyroid surgery were randomized and 29 patients completed the study. After randomization, patients undergoing thyroid surgery were allocated to two groups: one with an abrupt discontinuation of remifentanil after surgery and one with a gradual withdrawal of remifentanil after surgery. The primary outcome was the initial post-operative demand of analgesic medication., Results: Gradual withdrawal of remifentanil was associated with a delayed initial post-operative demand of analgesic medication (P = 0.006). The first morphine bolus was given after 76.3 +/- 89.0 min in the group with a gradual withdrawal of remifentanil versus after 9.0 +/- 13.5 min in the group with an abrupt discontinuation of remifentanil. However, overall morphine consumption, numeric rating scale scores, Ramsay Sedation Scale scores, and quality of recovery scores (QoR-40) were similar in both groups (P > 0.05)., Conclusion: Though overall morphine consumption, numeric rating scale scores, Ramsay Sedation Scale scores, and quality of recovery scores (QoR-40) are not altered, a gradual withdrawal of remifentanil after thyroid surgery is safe and associated with a delayed initial post-operative demand of analgesic drugs. The withdrawal process does, however, require vigilance and training., Trial Registration: Clinicaltrials.gov NCT03110653 (PI: Luc Barvais; date of registration: 03/31/2017).

Study Objectives: The aim of the present study was to assess the quality of recovery from anesthesia in patients undergoing laparoscopic cholecystectomy (LC) under total intravenous anesthesia, who received either methadone or morphine for post-surgical analgesia by means of questionnaire Quality of Recovery-40 (QoR-40)., Design: Prospective Randomized Clinical Trial., Setting: The setting was at an operating room, postoperative recovery area and hospital ward., Patients: Seventy patients who underwent LC under remifentanil-based anesthesia were randomly assigned to receive methadone 0.1 mg kg -1 or morphine 0.1 mg kg -1 ., Measurements: The primary outcome was the quality of recovery, using the Quality of Recovery Questionnaire (QoR-40). Secondary outcomes included time to eye opening, the occurrence of nausea and vomiting, pain score, use of supplemental analgesics, and PACU length of stay., Main Results: No differences were observed in the total or individual QoR-40 dimension scores. During the PACU stay, the occurrence of PONV and pain scores were similar between groups. Opioid consumption (p < 0.02) and the level of sedation (p < 0.01) were higher in the morphine group. There were no differences in the amount of time required to achieve PACU discharge criteria. The frequency of nausea or emesis, the severity of pain, and tramadol consumption were comparable between both groups while on the ward., Conclusions: Pain scores and the Quality of Recovery did not differ between patients who underwent LC under total intravenous anesthesia, who received either methadone or morphine for post-surgical analgesia., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The widespread use of remifentanil during total intravenous anesthesia (TIVA) has raised concerns about the risk of postoperative remifentanil-associated pain. Although a recent meta-analysis suggests that remifentanil-associated pain is unlikely to occur in patients with TIVA because of the protective effect of co-administered propofol, the evidence is not conclusive. We retrospectively assessed 635 patients who received robotic thyroid surgery under TIVA to evaluate the risk of remifentanil-associated pain. Postoperative pain was evaluated using 11-point numeric rating scale (NRS). Time dependent Cox proportional hazards regression analysis was used to determine the risk factors of treatment-requiring pain (NRS > 4) during the first 48 postoperative hours. Postoperative pain rapidly decreased, and treatment-requiring pain remained in 12.8% (81 out of 635) of patients at 48 hours postoperatively. After adjusting for the time-dependent analgesic consumption, intraoperative use of remifentanil > 0.2 mcg/kg/min was a positive predictor of postoperative pain with a hazard ratio of 1.296 (95% C.I., 1.014-1.656, P = 0.039) during 48 hours after surgery. In conclusion, excessive use of remifentanil during TIVA was associated with increased risk of pain after robotic thyroid surgery. Prospective trials are required to confirm these results and determine whether decreasing remifentanil consumption below the threshold can reduce postoperative pain., Competing Interests: The authors have declared that no competing interests exist.

Background: With the development of painless diagnosis and treatment, remifentanil, a synthetic opioid agonist, is increasingly used in gastroscopy for its rapid, short-term, and potent analgesic effect. However, the dosage of remifentanil used in endoscopy is unclear. Index of consciousness (IOC) is a new anesthesia depth-monitoring indicator that can be divided into index of consciousness 1 (IOC 1 ) and index of consciousness 2 (IOC 2 ); IOC 1 is used for estimating a patient's sedation state, whereas IOC 2 reflects analgesic depth. We hypothesized that combining with IOC 1 and IOC 2 monitoring may be helpful to identify an optimal remifentanil dosage in gastroscopic polypectomy., Methods: One hundred twenty patients scheduled for gastroscopic polypectomy were enrolled and were randomly assigned to remifentanil 2 ng/mL (group R2), 4 ng/mL (group R4), or 6 ng/mL (group R6), and 40 cases were in each group. During the anesthesia period, remifentanil was kept at the initial given concentration but propofol was adjusted according to IOC 1 . The primary outcomes were the dosage of propofol and remifentanil. The secondary outcomes were the variety of IOC 1 and IOC 2 , patients' awakening time, and peri-operative adverse reactions such as hypotension, hypertension, bradycardia, tachycardia, body movements, hypoxemia, therapy interruption, nausea, vomiting, aspiration, and intra-operative awareness., Results: With the increasing dosage of remifentanil, the propofol dosage and patients' awakening time decreased significantly, the morbidity of hypertension and body movements also declined, but the incidence of hypotension, bradycardia, and hypoxemia rose. In group R2, the value of IOC 2 remained above 50 during the treatment. However, IOC 2 dropped to below 30 at the beginning of the gastroscopy in group R6, and there was statistical difference in hypoxemia between groups R2 and R6 (P <0.05)., Conclusions: With the help of IOC monitoring, we found that a target concentration of remifentanil 4 ng/mL is comparatively ideal in patients under gastroscopic polypectomy., Trial Registration: Chinese Clinical Trial Register: ChiCTR-OOD-16009489 , on October 19, 2016.

Background: Intraoperative use of a high-dose remifentanil may induce postoperative hyperalgesia. Low-dose naloxone can selectively reverse some adverse effects of opioids without compromising analgesia. We thus hypothesized that the intraoperative use of a high-dose remifentanil combined with a low-dose naloxone infusion reduces postoperative hyperalgesia compared with the use of remifentanil alone., Methods: Patients undergoing elective thyroid surgery were randomly assigned into one of three groups, depending on the intraoperative effect-site concentration of remifentanil, with or without a continuous infusion of naloxone: 4 ng ml-1 remifentanil with 0.05 μg kg-1 h-1 naloxone in the high-remifentanil with naloxone group, and 4 or 1 ng ml-1 remifentanil with a placebo in the high- or low-remifentanil groups, respectively. We measured the pain thresholds (primary outcome) to mechanical stimuli using von Frey filaments and incidence of hyperalgesia on the peri-incisional area 24 h after surgery. We also measured pain intensity, analgesic consumptions and adverse events up to 48 h after surgery., Results: The pain threshold presented as von Frey numbers [median (interquartile range)] was significantly lower in the high-remifentanil group (n=31) than in the high-remifentanil with naloxone (n=30) and the low-remifentanil (n=30) groups [3.63 (3.22-3.84) vs 3.84 (3.76-4.00) vs 3.80 (3.69-4.08), P=0.011]. The incidence of hyperalgesia was also higher in the high-remifentanil group than in the other groups [21/31 vs 10/30 vs 9/30, P=0.005]. Postoperative pain intensity, analgesic consumptions and adverse events were similar between groups., Conclusions: The intraoperative use of low-dose naloxone combined with high-dose remifentanil reduced postoperative hyperalgesia but not pain., Clinical Trial Registration: NCT02856087., (© The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Background: Postoperative secondary hyperalgesia arises from central sensitization due to pain pathways facilitation and/or acute opioid exposure. The latter is also known as opioid-induced hyperalgesia (OIH). Remifentanil, a potent μ-opioid agonist, reportedly induces postoperative hyperalgesia and increases postoperative pain scores and opioid consumption. The pathophysiology underlying secondary hyperalgesia involves N-methyl-D-aspartate (NMDA)-mediated pain pathways. In this study, we investigated whether perioperatively infusing low-dose buprenorphine, an opioid with anti-NMDA activity, in patients receiving remifentanil infusion prevents postoperative secondary hyperalgesia., Methods: Sixty-four patients, undergoing remifentanil infusion during general anaesthesia and major lung surgery, were randomly assigned to receive either buprenorphine i.v. infusion (25 μg h-1 for 24 h) or morphine (equianalgesic dose) perioperatively. The presence and extent of punctuate hyperalgesia were assessed one day postoperatively. Secondary outcome variables included postoperative pain scores, opioid consumption and postoperative neuropathic pain assessed one and three months postoperatively., Results: A distinct area of hyperalgesia or allodynia around the surgical incision was found in more patients in the control group than in the treated group. Mean time from extubation to first morphine rescue dose was twice as long in the buprenorphine-treated group than in the morphine-treated group: 18 vs 9 min (P=0.002). At 30 min postoperatively, patients receiving morphine had a higher hazard ratio for the first analgesic rescue dose than those treated with buprenorphine (P=0.009). At three months, no differences between groups were noted., Conclusions: Low-dose buprenorphine infusion prevents the development of secondary hyperalgesia around the surgical incision but shows no long-term efficacy at three months follow-up., (© The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia.)