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Background: The intraoperative autonomic neural blockade (ANB) was found safe and effective in controlling pain and associated symptoms and reducing analgesic consumption after laparoscopic sleeve gastrectomy (LSG). This study evaluated whether ANB performed at the outset of LSG reduces anesthetic consumption and promotes hemodynamic stability., Methods: This prospective, double-blinded, randomized trial involved patients undergoing LSG in 2 high-volume institutions. Patients were randomized to receive ANB either at the onset or the end of the procedure. The primary outcome measure was the consumption of remifentanil and sevoflurane. Secondary outcomes included Aldrete scale score differences in the recovery room and hemodynamic stability during the surgery., Results: In total, 80 patients (40 in the ANB at the onset group and 40 in the control group) were included for analysis. The consumption of remifentanil was significantly lower in the onset group compared to the control group (mean difference -0.04 mcg/kg/min, 95% confidence interval [CI], -0.06 to -0.02; P < .0001). There were no differences in the Aldrete scale scores between the 2 groups. Mean heart rate (HR) and mean arterial pressure (MAP) were also significantly less during surgery in the ANB at the onset group. No complications related to the ANB occurred., Conclusions: Performing ANB at the onset of LSG is a safe and effective approach that reduces remifentanil consumption and promotes hemodynamic stability during the procedure. This technique holds promise for optimizing anesthesia management in LSG and other minimally invasive surgeries., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.)

Background: Remifentanil, an ultra-short-acting µ-opioid receptor agonist, is commonly used for anesthetic management due to excellent adjustability. Remifentanil is known to cause sinus bradycardia, however, because it has a direct negative chronotropic effect on the cardiac conduction system and there is an indirect negative chronotropic effect via the parasympathetic nervous system., Case Presentation: An 8-year-old Japanese boy was diagnosed with acute hydrocephalus due to a brain tumor in the fourth ventricle and underwent emergency surgery. Imaging examination showed brainstem compression. Endoscopic third ventriculostomy and ventriculoperitoneal shunt surgery were scheduled. Remifentanil was started during induction of general anesthesia, but electrocardiogram showed sinus bradycardia, then Wenckebach-type atrioventricular block, and then complete atrioventricular block. Remifentanil was immediately discontinued, and we administered atropine sulfate. Complete atrioventricular block was restored to sinus rhythm. When remifentanil was restarted, however, the electrocardiogram again showed sinus bradycardia, Wenckebach-type atrioventricular block, and then complete atrioventricular block. Remifentanil was again immediately discontinued, we administered adrenaline, and then complete atrioventricular block was restored to sinus rhythm. Fentanyl was used instead of remifentanil with continuous infusion of dopamine. There has since been no further occurrence of complete atrioventricular block., Conclusions: This is the first known case of complete atrioventricular block in a pediatric patient with increased intracranial pressure seemingly caused by administration of remifentanil., (© 2024. The Author(s).)

Remifentanil-induced hyperalgesia (RIH) is a part of a general opioid-induced hyperalgesia (OIH) syndrome, seemingly resulting from abrupt cessation of continuous remifentanil infusion at rates equal or exceeding 0.3 mcg/kg/min. The intricate mechanisms of its development are still not completely understood. However, hyperactivation of the N -methyl d -aspartate receptor system, descending spinal facilitation and increased concentration of dynorphin (a κ-opioid ligand) are commonly proposed as possible mechanisms. Several ways of prevention and management have been suggested, such as slow withdrawal of remifentanil infusion, the addition of propofol, pretreatment with or concomitant administration of ketamine, buprenorphine, cyclooxygenase-2 inhibitors (NSAIDs), methadone, dexmedetomidine. In clinical and animal studies, these strategies exhibited varying success, and many are still being investigated., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The occurrence of hypotension after induction of general anaesthesia is common in geriatric patients, and should be prevented to minimise perioperative complications. Compared with propofol, remimazolam potentially has a lower incidence of hypotension. This study aimed to compare the incidence of hypotension after general anaesthesia induction with remimazolam or propofol in geriatric patients., Methods: This single-centre, double-blind, randomised trial enrolled 90 patients aged ≥80 yr who received general anaesthesia for scheduled surgery. Patients were randomised to receive remimazolam (12 mg kg -1 h -1 ) or propofol (0.025 mg kg -1 s -1 ) for anaesthesia induction, with remifentanil and sevoflurane. The presence or absence of hypertension on the ward served as the stratification factor. The incidence of hypotension after the induction of general anaesthesia, defined as a noninvasive mean arterial pressure of <65 mm Hg measured every minute from initiation of drug administration to 3 min after tracheal intubation, was the primary outcome. Subgroup analysis was performed for the primary outcome using preoperative ward hypertension, clinical frailty scale, Charlson Comorbidity Index, and age., Results: Three subjects were excluded before drug administration, and 87 subjects were included in the analysis. The incidence of hypotension was 72.1% (31/43) and 72.7% (32/44) with remimazolam or propofol, respectively. No statistically significant differences (adjusted odds ratio, 0.96; 95% confidence interval, 0.37-2.46; P=0.93) were observed between groups. Subgroup analysis revealed no significant differences between groups., Conclusions: Compared with propofol, remimazolam did not reduce the incidence of hypotension after general anaesthesia induction in patients aged ≥80 yr., Clinical Trial Registration: UMIN000042587., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Serotonin syndrome (SS) is a life-threatening condition caused by serotonergic medications. We describe a unique case of SS likely caused by prolonged exposure to propofol and remifentanil alone. A young male presented for vestibular schwannoma resection. Several hours into the case, the patient demonstrated hyperthermia and hemodynamic instability, followed by clonus, rigidity, shivering, and tachycardia after emergence. SS was diagnosed using Hunter's criteria and improved with supportive measures. While the patient endorsed a history of methamphetamine use, his urine drug screen was negative. The possibility of SS should be considered when administering propofol and remifentanil, particularly with prolonged infusions., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

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.)

Study Objective: To estimate the incidence of unwanted spontaneous responsiveness and burst suppression (BSupp) in patients undergoing state entropy (SE) and surgical pleth index (SPI)-guided total intravenous anesthesia (TIVA) with target-controlled infusion (TCI)., Design: Observational, prospective, single-center study., Settings: Operating room., Patients: 107 adult (<65 years) and elderly (≥65 years) women undergoing breast surgery., Interventions: Propofol-remifentanil TIVA-TCI-guided by SE for depth of anesthesia monitoring (target value 40-60) and SPI for antinociception monitoring (target value 20-50) without neuromuscular blockade., Measurements: Age; body mass index; American Society of Anesthesiologists physical status classification; concentration at the effect site of propofol (CeP) and remifentanil (CeR) at loss of responsiveness (LoR), median during anesthesia maintenance (MdM), and at return of responsiveness (RoR); propofol infusion duration; incidence of postoperative delirium (POD) with Confusing Assessment Method for the Intensive Care Unit., Main Results: During SE-SPI-guided TIVA-TCI, 13.1% of patients showed unwanted spontaneous responsiveness, whereas 45.8% showed BSupp. Unwanted spontaneous responsiveness was observed mainly in adults (p < 0.05), and higher CeP RoR (p < 0.05) was registered. BSupp was observed mainly in patients showing a lower CeP MdM (p < 0.01) and CeP RoR (p < 0.05). Unwanted spontaneous responsiveness and BSupp were not associated with significant differences in CeRs. An age-related hysteresis effect was observed, resulting in higher CeP LoR than CeP RoR (p < 0.001). 12.2% of patients showed POD. Only preoperative serum albumin was associated with increased likelihood of POD (p = 0.046)., Conclusions: The SE-SPI-guided TIVA-TCI did not prevent unwanted spontaneous responsiveness and BSupp. CeP RoR may be used as a proxy for anesthetic sensitivity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The liberal use of remifentanil in spine surgery has been associated with an increased incidence of postoperative hyperalgesia. Nevertheless, controversies remain as the existing evidence is inconclusive to determine the relationship between remifentanil use and the development of opioid-induced hyperalgesia. We hypothesized that intraoperative infusion of higher dose remifentanil during scoliosis surgery is associated with postoperative hyperalgesia, manifesting clinically as greater postoperative morphine consumption and pain scores., Methods: Ninety-seven patients with adolescent idiopathic scoliosis (AIS) who underwent posterior spinal fusion surgery at a single tertiary institution from March 2019 until June 2020 were enrolled in this retrospective study. Anesthesia was maintained using a target-controlled infusion of remifentanil combined with volatile anesthetic desflurane in 92 patients, while five patients received it as part of total intravenous anesthesia. Intravenous ketamine, paracetamol, and fentanyl were administered as multimodal analgesia. All patients received patient-controlled analgesia (PCA) morphine postoperatively. Pain scores at rest and on movement, assessed using the numerical rating scale, and the cumulative PCA morphine consumption were collected at a six-hourly interval for up to 48 h. According to the median intraoperative remifentanil dose usage of 0.215 µg/kg/min, patients were divided into two groups: low dose and high dose group., Results: There were no significant differences in the pain score and cumulative PCA morphine consumption between the low and high dose remifentanil group. The mean duration of remifentanil infusion was 134.9 ± 22.0 and 123.4 ± 23.7 min, respectively., Conclusion: Intraoperative use of remifentanil as an adjuvant in AIS patients undergoing posterior spinal fusion surgery was not associated with postoperative hyperalgesia., (© 2023. The Author(s).)

Importance: It is uncertain whether a rapid-onset opioid is noninferior to a rapid-onset neuromuscular blocker during rapid sequence intubation when used in conjunction with a hypnotic agent., Objective: To determine whether remifentanil is noninferior to rapid-onset neuromuscular blockers for rapid sequence intubation., Design, Setting, and Participants: Multicenter, randomized, open-label, noninferiority trial among 1150 adults at risk of aspiration (fasting for <6 hours, bowel occlusion, recent trauma, or severe gastroesophageal reflux) who underwent tracheal intubation in the operating room at 15 hospitals in France from October 2019 to April 2021. Follow-up was completed on May 15, 2021., Interventions: Patients were randomized to receive neuromuscular blockers (1 mg/kg of succinylcholine or rocuronium; n = 575) or remifentanil (3 to 4 μg/kg; n = 575) immediately after injection of a hypnotic., Main Outcomes and Measures: The primary outcome was assessed in all randomized patients (as-randomized population) and in all eligible patients who received assigned treatment (per-protocol population). The primary outcome was successful tracheal intubation on the first attempt without major complications, defined as lung aspiration of digestive content, oxygen desaturation, major hemodynamic instability, sustained arrhythmia, cardiac arrest, and severe anaphylactic reaction. The prespecified noninferiority margin was 7.0%., Results: Among 1150 randomized patients (mean age, 50.7 [SD, 17.4] years; 573 [50%] women), 1130 (98.3%) completed the trial. In the as-randomized population, tracheal intubation on the first attempt without major complications occurred in 374 of 575 patients (66.1%) in the remifentanil group and 408 of 575 (71.6%) in the neuromuscular blocker group (between-group difference adjusted for randomization strata and center, -6.1%; 95% CI, -11.6% to -0.5%; P = .37 for noninferiority), demonstrating inferiority. In the per-protocol population, 374 of 565 patients (66.2%) in the remifentanil group and 403 of 565 (71.3%) in the neuromuscular blocker group had successful intubation without major complications (adjusted difference, -5.7%; 2-sided 95% CI, -11.3% to -0.1%; P = .32 for noninferiority). An adverse event of hemodynamic instability was recorded in 19 of 575 patients (3.3%) with remifentanil and 3 of 575 (0.5%) with neuromuscular blockers (adjusted difference, 2.8%; 95% CI, 1.2%-4.4%)., Conclusions and Relevance: Among adults at risk of aspiration during rapid sequence intubation in the operating room, remifentanil, compared with neuromuscular blockers, did not meet the criterion for noninferiority with regard to successful intubation on first attempt without major complications. Although remifentanil was statistically inferior to neuromuscular blockers, the wide confidence interval around the effect estimate remains compatible with noninferiority and limits conclusions about the clinical relevance of the difference., Trial Registration: ClinicalTrials.gov Identifier: NCT03960801.

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.

Dexmedetomidine is an α 2 agonist and remifentanil is a short-acting μ opioid agonist. We aimed to compare the dexmedetomidine and remifentanil infusions used for conscious sedation in geriatric patients undergoing outpatient cataract surgery in terms of sedation quality, side effects, and surgeon satisfaction. Eighty patients were allocated into two groups as per the administration of dexmedetomidine (dexmedetomidine group) and remifentanil (remifentanil group) infusion in this randomized, prospective, double-blinded study. In dexmedetomidine group (n = 40), after a loading of 1 μg/kg dexmedetomidine in 10 minutes, 0.4 μg/kg/h infusion was administered. In the remifentanil group (n = 40), remifentanil at a dose of 0.05 μg/kg was administered for 10 minutes, and then 0.05 μg/kg/min infusion was continued. Observer Assessment Warning/Sedation Scale values evaluating sedation quality were lower in the dexmedetomidine group than in the remifentanil group, although it was not statistically significant (P > 0.05). Bispectral Index values evaluating sedation quality were lower in the dexmedetomidine group according to the remifentanil group (P < 0.05). The dexmedetomidine group had lower Verbal Rating Scale and Visual Analogue Scale scores evaluating pain intensity compared with the remifentanil group (P < 0.05). The nausea Visual Analogue Scale values evaluating the severity of postoperative nausea in the dexmedetomidine group were lower than those in the remifentanil group (P < 0.05). The surgeon satisfaction was found to be greater in the dexmedetomidine group compared with the remifentanil group (P = 0.015). In geriatric patients, the targeted sedation and analgesia levels were achieved more easily with dexmedetomidine infusion, without hemodynamic and respiratory side effects, compared to remifentanil infusion., Competing Interests: None

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: The purpose of this study was to evaluate the efficacy and safety of sevoflurane-remifentanil (SR) vs propofol-remifentanil (PR) as inhalation anesthesia or total intravenous anesthesia in patients undergoing craniotomy, respectively., Methods: Electronic databases included PubMed, ScienceDirect, Embase, Cochrane library, CNKI, and Wanfang data were searched using suitable search items. Randomized clinical controlled trials comparing the combination of SR and PR as anesthetics for neurosurgery were included. The outcomes included wake-up time, spontaneous respiration time, extubation time, and safety., Results: Seventeen studies were included in this meta-analysis. There were no statistically significant differences in wake-up time (P = .25, standardized mean difference (SMD) = 0.29, 95% CI -0.20 to 0.77), extubation time (P = .1, SMD = 0.52, 95% CI -0.11 to 1.14) and spontaneous respiration time (P = .58, SMD = 0.43, 95% CI -1.07 to 1.93) when patients with SF and PF for anesthesia maintenance. Moreover, the changes of hemodynamic parameters are similar between the 2 groups. During anesthesia maintenance, SF could significantly increase the incidence of hypotension and brain edema than PF (P = .02, SMD = 1.68, 95% CI 1.07 to 2.62; P < .0001, SMD = 3.37, 95% CI 1.86 to 6.12), PF markedly promoted the incidence of hypertension (P = .001, SMD = 0.55, 95% CI 0.39 to 0.79). The postoperative adverse reactions were similar between the 2 groups (P > .05), but the incidence of postoperative nausea and vomiting proved to be higher in SF group (P < .0001, SMD = 2.12, 95% CI 1.47 to 3.07)., Conclusions: SR and PR as anesthetics in patients underwent craniotomy had similar effects, but PR was superior to SR in terms of safety of intraoperation and postoperation., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Study Objective: The main objective of this study is to test the feasibility of the local anesthetic (LA) Mepivacaine 1% and sedation with Remifentanil as the primary anesthetic technique for the insertion of a peritoneal dialysis (PD) catheter, without the need to convert to general anesthesia., Methods: We analyzed 27 consecutive end-stage renal disease (ESRD) patients who underwent the placement of a peritoneal catheter at our center between March 2015 and January 2019. The procedures were all performed by a general or vascular surgeon, and the postoperative care and follow-up were all conducted by the same peritoneal dialysis team., Results: All of the 27 subjects successfully underwent the procedure without the need of conversion to general anesthesia. The catheter was deemed prone to usage in all patients and was found to be leak-proof in 100% of the patients., Conclusion: This study describes a safe and successful approach for insertion of a PD catheter by combined infiltration of the local anesthetic Mepivacaine 1% and sedation with Remifentanil. Hereby, ESRD patients can be treated without general anesthesia, while ensuring functionality of the PD catheter., Competing Interests: The authors have declared that no competing interests exist.

Background: Closed-loop control of propofol-remifentanil anesthesia using the processed electroencephalography depth-of-hypnosis index provided by the NeuroSENSE monitor (WAVCNS) has been previously described. The purpose of this placebo-controlled study was to evaluate the performance (percentage time within ±10 units of the setpoint during the maintenance of anesthesia) of a closed-loop propofol-remifentanil controller during induction and maintenance of anesthesia in the presence of a low dose of ketamine., Methods: Following ethical approval and informed consent, American Society of Anesthesiologist (ASA) physical status I-II patients aged 19-54 years, scheduled for elective orthopedic surgery requiring general anesthesia for >60 minutes duration, were enrolled in a double-blind randomized, placebo-controlled, 2-group equivalence trial. Immediately before induction of anesthesia, participants in the ketamine group received a 0.25 mg·kg-1 bolus of intravenous ketamine over 60 seconds followed by a continuous 5 µg·kg-1·min-1 infusion for up to 45 minutes. Participants in the control group received an equivalent volume of normal saline. After the initial study drug bolus, closed-loop induction of anesthesia was initiated; propofol and remifentanil remained under closed-loop control until the anesthetic was tapered and turned off at the anesthesiologist's discretion. An equivalence range of ±8.99% was assumed for comparing controller performance., Results: Sixty patients participated: 41 males, 54 ASA physical status I, with a median (interquartile range [IQR]) age of 29 [23, 38] years and weight of 82 [71, 93] kg. Complete data were available from 29 cases in the ketamine group and 27 in the control group. Percentage time within ±10 units of the WAVCNS setpoint was median [IQR] 86.6% [79.7, 90.2] in the ketamine group and 86.4% [76.5, 89.8] in the control group (median difference, 1.0%; 95% confidence interval [CI] -3.6 to 5.0). Mean propofol dose during maintenance of anesthesia for the ketamine group was higher than for the control group (median difference, 24.9 µg·kg-1·min-1; 95% CI, 6.5-43.1; P = .005)., Conclusions: Because the 95% CI of the difference in controller performance lies entirely within the a priori equivalence range, we infer that this analgesic dose of ketamine did not alter controller performance. Further study is required to confirm the finding that mean propofol dosing was higher in the ketamine group, and to investigate the implication that this dose of ketamine may have affected the WAVCNS., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2021 International Anesthesia Research Society.)

Opioid use disorder (OUD) has a variety of adverse effects on both the users and their offspring. In the current study, a random group of Sprague-Dawley rats (25 females and 15 males) were tested for intravenous self-administration of the opioid agonist remifentanil to determine the range of acquisition for opioid. One-month after the end of self-administration of remifentanil, rats with the highest intake were mated together and rats with lowest intake were mated together. Then, the offspring of the two groups were tested for anxiety-like behavior, locomotor activity, nociception and intravenous remifentanil self-administration. The parents showed a range of remifentanil self-administration, especially in the female rats. The offspring of the parents with low and high remifentanil self-administration showed significant differences in specific behavioral functions. On the hotplate test of nociception, the female offspring parents with high remifentanil self-administration had significantly longer hotplate latencies, indicating reduced nociception, than the female offspring of parents with low remifentanil-self-administration, whereas there was no difference in the male offspring of low and high responding parents. In the elevated plus maze test of anxiety-like behavior, the offspring of the parents with high remifentanil intake showed more anxiety-like behavior than the offspring of the parents with low remifentanil intake regardless of sex. Locomotor activity was not significantly different. Interestingly, no significant differences in remifentanil self-administration in the offspring of parents with low and high remifentanil self-administration were detected. Overall, our data suggest a considerable range in remifentanil self-administration in rats and the offspring of rats with high opioid self-administration exhibit different behaviors vs offspring of rats with low opioid self-administration., (Copyright © 2021. Published by Elsevier B.V.)

Background: The aim of the study was to investigate whether closed-loop compared to manual bispectral index (BIS)-guided target-controlled infusion of propofol and remifentanil could decrease the incidence of postoperative neurocognitive disorders after elective major noncardiac surgery., Methods: Patients aged >50 admitted for elective major noncardiac surgery were included in a single-blind randomized (ratio 2:1) trial. The anesthetic protocol was allocated by randomization into either closed-loop or manual BIS-guided propofol and remifentanil titration. The BIS target range was 40-60. All patients had cognitive assessment the day before surgery and within 72 hours after surgery using a battery of neuropsychological tests. The primary outcome was the rate of postoperative neurocognitive disorders. Postoperative neurocognitive disorders were defined as a decrease >20% from baseline on at least 3 scores. Intergroup comparison of the primary outcome was performed using the χ2 test., Results: A total of 143 and 61 patients were included in the closed-loop and manual groups, respectively (age: 66 [8] vs 66 [9] years). The primary outcome was observed in 18 (13%) and 10 (16%) patients of the closed-loop and manual groups, respectively (relative risk [95% confidence interval {CI}], 0.77 [0.38-1.57], P = .47). Intraoperative propofol consumption was lower (4.7 [1.4] vs 5.7 [1.4] mg·kg-1·h-1, mean difference [MD] [95% CI], -0.73 [-0.98 to -0.48], P < .0001) and the proportion of time within the BIS target range higher (84 [77-89] vs 74 [54-81]%, MD [95% CI], 0.94 [0.67-1.21], P < .0001) in the closed-loop group., Conclusions: Closed-loop compared to manual BIS-guided total intravenous anesthesia provided a significant reduction in episodes of an excessive depth of anesthesia while decreasing intraoperative propofol requirement but no evidence for a reduction of the incidence of postoperative neurocognitive disorders after elective major noncardiac surgery was observed., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2020 International Anesthesia Research Society.)

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.)

Background: Recent studies showed partial reversal of opioid-induced respiratory depression in the pre-Bötzinger complex and the parabrachial nucleus/Kölliker-Fuse complex. The hypothesis for this study was that opioid antagonism in the parabrachial nucleus/Kölliker-Fuse complex plus pre-Bötzinger complex completely reverses respiratory depression from clinically relevant opioid concentrations., Methods: Experiments were performed in 48 adult, artificially ventilated, decerebrate rabbits. The authors decreased baseline respiratory rate ~50% with intravenous, "analgesic" remifentanil infusion or produced apnea with remifentanil boluses and investigated the reversal with naloxone microinjections (1 mM, 700 nl) into the Kölliker-Fuse nucleus, parabrachial nucleus, and pre-Bötzinger complex. In another group of animals, naloxone was injected only into the pre-Bötzinger complex to determine whether prior parabrachial nucleus/Kölliker-Fuse complex injection impacted the naloxone effect. Last, the µ-opioid receptor agonist [d-Ala,2N-MePhe,4Gly-ol]-enkephalin (100 μM, 700 nl) was injected into the parabrachial nucleus/Kölliker-Fuse complex. The data are presented as medians (25 to 75%)., Results: Remifentanil infusion reduced the respiratory rate from 36 (31 to 40) to 16 (15 to 21) breaths/min. Naloxone microinjections into the bilateral Kölliker-Fuse nucleus, parabrachial nucleus, and pre-Bötzinger complex increased the rate to 17 (16 to 22, n = 19, P = 0.005), 23 (19 to 29, n = 19, P < 0.001), and 25 (22 to 28) breaths/min (n = 11, P < 0.001), respectively. Naloxone injection into the parabrachial nucleus/Kölliker-Fuse complex prevented apnea in 12 of 17 animals, increasing the respiratory rate to 10 (0 to 12) breaths/min (P < 0.001); subsequent pre-Bötzinger complex injection prevented apnea in all animals (13 [10 to 19] breaths/min, n = 12, P = 0.002). Naloxone injection into the pre-Bötzinger complex alone increased the respiratory rate to 21 (15 to 26) breaths/min during analgesic concentrations (n = 10, P = 0.008) but not during apnea (0 [0 to 0] breaths/min, n = 9, P = 0.500). [d-Ala,2N-MePhe,4Gly-ol]-enkephalin injection into the parabrachial nucleus/Kölliker-Fuse complex decreased respiratory rate to 3 (2 to 6) breaths/min., Conclusions: Opioid reversal in the parabrachial nucleus/Kölliker-Fuse complex plus pre-Bötzinger complex only partially reversed respiratory depression from analgesic and even less from "apneic" opioid doses. The lack of recovery pointed to opioid-induced depression of respiratory drive that determines the activity of these areas., (Copyright © 2021, the American Society of Anesthesiologists. All Rights Reserved.)

BACKGROUND Volatile anesthesia possesses cardioprotective properties, and it is widely used in patients undergoing coronary artery bypass surgery, but no randomized controlled trials (RCTs) are available on the use of sevoflurane-remifentanil versus propofol-remifentanil anesthesia for patients with coronary artery disease (CAD) during noncardiac surgery. This study was designed to compare the 2 different types of general anesthesia in patients with CAD undergoing noncardiac surgery at a single center. MATERIAL AND METHODS Patients with CAD undergoing noncardiac surgery were enrolled in an RCT conducted between March 2016 and December 2017. The participants were randomized to receive either sevoflurane-remifentanil or propofol-remifentanil anesthesia. The primary endpoint was occurrence of in-hospital cardiovascular events. The secondary endpoints included delirium, postoperative nausea and vomiting (PONV), Intensive Care Unit (ICU) length of stay (LOS), in-hospital morbidity and mortality, and hospital LOS. RESULTS A total of 164 participants completed the study (sevoflurane: 81; propofol: 83). The occurrence of in-hospital cardiovascular events did not differ between the 2 groups (42.6% vs 39.4%, P=0.86). The occurrence of delirium did not differ between the 2 groups after the operation. PONV had a higher frequency after sevoflurane anesthesia at 48 h compared with propofol. In-hospital morbidity and mortality, ICU LOS, and hospital LOS were similar between the 2 groups (all P>0.05). At 30 days after surgery, no between-group differences in cardiac morbidity and mortality were observed. CONCLUSIONS In this study, anesthesia using sevoflurane-remifentanil did not provide additional postoperative cardioprotection in comparison with propofol-remifentanil in patients with CAD undergoing noncardiac surgery.

Intravenous drug self-administration remains the 'gold standard' for assessing abuse liability. Failure of a drug to maintain self-administration might indicate the absence of positive reinforcing effects but might also indicate the presence of aversive effects. Sensitivity to aversive and punishing effects of drugs (as well as nondrug stimuli) might collectively determine the likelihood of use, abuse and relapse. Using a choice procedure, this study compared the effects of remifentanil (mu opioid receptor agonist; 0.001-0.01 mg/kg/infusion) and histamine (H1-4 receptor agonist; 0.32-3.2 mg/kg/infusion), alone and in mixtures, to test the hypothesis that remifentanil/histamine mixtures are less reinforcing compared with remifentanil alone and less punishing compared with histamine alone. Male Sprague-Dawley rats (n = 10) chose between an intravenous infusion + a pellet and a pellet alone. Rats were indifferent to saline, chose remifentanil + a pellet over a pellet alone, and chose a pellet alone over histamine + a pellet. The effects of remifentanil/histamine mixtures generally were different from the constituent doses of histamine alone but not from remifentanil alone. A mixture containing 3.2 mg/kg/infusion histamine and either 0.001 or 0.0032 mg/kg/infusion remifentanil was not different from saline but was different from the effects of the constituent dose, insofar as choice increased compared with 3.2 mg/kg/infusion histamine alone and decreased compared with 0.001 or 0.0032 mg/kg/infusion remifentanil alone. Reinforcing doses of remifentanil combined with punishing doses of histamine can yield mixtures that are neither preferred nor avoided, offering 'proof-of-principle' for using drug mixtures to avoid adverse effects of opioid receptor agonists., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Awake fiberoptic endoscope intubation (AFOI) is the primary strategy for managing anticipated difficult airways. Adequate sedation, most commonly being achieved with remifentanil and dexmedetomidine, is integral to this procedure. This meta-analysis aimed to compare the safety and efficacy of these 2 sedatives., Methods: We conducted electronic searches in Embase, Web of Science, PubMed, Google Scholar, Medline, Springer, and Web of Science with no language restrictions. Studies comparing safety and efficacy between the sole use of remifentanil and dexmedetomidine among patients who underwent AFOI were included. Eight randomized controlled trials, comprising 412 patients, met the inclusion criteria. The primary outcomes were first attempt intubation success rate and incidence of hypoxia. The secondary outcomes were the Ramsay Sedation Scale score at intubation, memory recall of endoscopy, and unstable hemodynamic parameters during intubation., Results: Dexmedetomidine significantly reduced the incidence of hypoxemia during AFOI (risk ratio: 2.47; 95% confidence [CI]: 1.32-4.64]) compared with remifentanil; however, the first intubation success rates were equivalent (risk ratio: 1.12; 95% CI: 0.87-1.46]. No significant differences between the 2 sedatives were found for the Ramsay Sedation Scale score at intubation (mean difference: -0.14; 95% CI: -0.66-0.38) or unstable hemodynamic parameters during intubation (risk ratio: 0.83; 95% CI: 0.59-1.17). Dexmedetomidine reduced memory recall of endoscopy (risk ratio: 1.39; 95% CI: 1.13-1.72)., Conclusions: While both remifentanil and dexmedetomidine are effective for AFOI and well-tolerated, dexmedetomidine may be more effective in reducing the incidence of hypoxemia and memory recall of endoscopy., Prosperp Registration Number: CRD42020169612., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

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.)

Background In most scenarios, anaesthesiologists titrate opioids to control nociceptive surgical stress based on intraoperative haemodynamic changes. Remifentanil was reported to cause more profound cardiovascular depression than sufentanil. A concern is that this direct cardiovascular depression might counteract the hypertension and tachycardia caused by surgical manipulation and mask inadequate analgesia. Objective To compare remifentanil and sufentanil, titrated to maintain a comparable haemodynamic range (within 20% of baseline) and combined with the same propofol regimen, in stress reduction measured as plasma levels of putative mediators of surgical stress. Setting Huashan Hospital of Fudan University, Shanghai, China. Method Forty-five patients undergoing supratentorial glioma resection were randomised to the remifentanil group or the sufentanil group. Main outcome measures Plasma concentrations of cortisol, epinephrine, norepinephrine, interleukin-6, interleukin-10 and lymphocyte counts were analysed before anaesthesia, 1 h after incision, at the end of surgery and 24 h after incision using enzyme-linked immunosorbent assay and an automatic haematology analyser. Recovery profiles during emergence from anaesthesia were also compared. Results Except for a lower epinephrine concentration in the remifentanil group 24 h after incision (median [interquartile range], 4.2 [3.4-6.1] vs. 8.4 [4.8-12.5] ng/ml; P = 0.003), stress biomarkers were not significantly different between the two groups. Patients in the sufentanil group had lower grades in coughing, restlessness (P = 0.001 and < 0.001, respectively) and a lower incidence of postoperative shivering (P = 0.007). Conclusion Compared to that of sufentanil, the direct cardiovascular depression of remifentanil does not mask the clinical manifestation of inadequate analgesia when both drugs are titrated according to haemodynamic variables in neurosurgery.

Background: In the University Medical Center Groningen in Groningen, the Netherlands, moderate-to-deep sedation is provided by nursing staff trained and supervised by the anesthesia department using protocol-based target-controlled infusions (TCIs) of propofol and remifentanil. The aim of this retrospective cohort study was to investigate the incidence of events with potential adverse health consequences within this service model and the risk factors for the occurrence of these events., Methods: We retrospectively interrogated a database containing the computerized anesthetic records of 2937 procedures where moderate-to-deep sedation was provided using TCI administration of propofol and remifentanil between May 2014 and October 2017. The primary outcome measures were the incidence of sedation-related events with potential adverse health consequences and risk factors for the occurrence of such events. The events under investigation were unplanned intensive care unit (ICU) admission, need for cardiopulmonary resuscitation (CPR), death on the day of the procedure due to sedation-related events, cardiovascular events (arrhythmias, hypertension, and hypotension), pulmonary events (aspiration, desaturation, unplanned tracheal intubation), anaphylactic or allergic reactions, and the termination of the procedure due to sedation-related events. Cardiovascular and pulmonary events were classified as severe, significant, or moderate. Events were identified by using computer algorithms to search the computerized records from all included procedures., Results: Data from 2937 procedures were analyzed. No patients suffered catastrophic events (death, need for CPR, or unplanned ICU admission). Thirty-two severe sedation-related events occurred in 32 procedures. Severe desaturation (0.6%; 95% confidence interval [CI], 0.4-0.9) and severe hypertension (0.2%; 95% CI, 0.04-0.37) were the most common severe events. Significant hypotension (8.8%; 95% CI, 7.73-9.77) and significant desaturation (1.6%; 95% CI, 1.12-2.02) were found to be the most common events with potential adverse health consequences. No patient suffered lasting health consequences. Average mean and maximum targeted effect-site concentrations (Cet) for propofol were 2.6 ± 0.83 and 3.3 ± 1.09 µg·mL, respectively, and for remifentanil 0.84 ± 0.18 and 0.99 ± 0.22 ng·mL, respectively. Maximum Cets of propofol were lower among patients with higher body mass index (BMI) and were higher among patients of younger age. Higher BMI was a risk factor for desaturation. Increased age and lower BMI were risk factors for hypotension. Longer procedure time was a risk factor for both desaturation and hypotension., Conclusions: Moderate-to-deep sedation by propofol and remifentanil TCI has a low incidence of catastrophic and severe events.

Objectives: One of the most prevalent complications of orthotopic liver transplant is primary graft dysfunction. Recent studies have shown the preconditioning effect of remifentanil on animal livers but not human livers. Here, we compared the preconditioning effects of remifentanil and fentanyl in orthotopic liver transplant in human patients., Materials and Methods: In this double-blind clinical trial, 100 patients who underwent liver transplant from deceased donors were randomly allocated into 2 groups. Patients in the remifentanil group received remifentanil infusion, and those in the fentanyl group received fentanyl infusion during maintenance of anesthesia. Serum aminotransferase levels, prothrombin time (international normalized ratio), partial thrombin time, arterial blood gas levels, and renal function tests were evaluated over 7 days posttransplant. Intensive care unit stay and hospitalization were also recorded., Results: The median peak alanine aminotransferase level during 7 days after transplant was 2100 U/L (interquartile range, 1230-3220) in the remifentanil group and 3815 U/L (interquartile range, 2385-5675) in the fentanyl group (P = .048). Metabolic acidosis, renal state, prothrombin time (international normalized ratio), and partial thrombin time were similar in both groups (P > .05). Durations of stay in the intensive care unit and hospital were not significantly different between the 2 groups (P = .75 and P = .23, respectively). Overall, the clinical outcomes were similar in the remifentanil and fentanyl groups (P > .05)., Conclusions: We found that remifentanil and fentanyl were not different with regard to their preconditioning effects and graft protection in orthotopic liver transplant recipients.

Background: The aim of this prospective randomized controlled study was to evaluate whether pretreatment with a small dose of dezocine could prevent remifentanil-induced cough in general anesthesia induction., Trial Design: a prospective, randomized, controlled study., Methods: A total of 210 patients receiving elective operative hysteroscopy from December 2018 to April 2019 were enrolled in the present study. They were randomly equally separated into dezocine group (n = 105) and control group (n = 105). Patients were intravenously pre-administrated with dezocine 0.03 mg/kg (diluted to 5 mL) or the same volume of normal saline 1 min prior to remifentanil infusion. One minute later, intravenous injection of propofol 1.5 mg/kg and cisatracurium 0.1 mg/kg were given to all patients for induction of general anesthesia. The counts of coughs occurred during the anesthesia induction period were recorded and the severity of cough was scaled., Results: There were 7 cases of mild cough in dezocine group and 18 cases of mild cough, 12 cases of moderate cough and 4 cases of severe cough in control group. The incidence rate of cough was significantly lower and the severity of cough was obviously relieved in dezocine group compared to control group (6.67% vs. 32.38%, P <  0.001). The two groups were not significantly different in heart rate and mean arterial pressure before the induction, before and after the intubation, and in operating time and postoperative visual analog scale pain scores., Conclusion: This study recommends the efficacy and safety of a pretreatment with a small dose of dezocine in reducing remifentanil-induced cough during general anesthesia., Trial Registration: ChiCTR2000032035 . Date of registration: Retrospectively registered on 2020/04/18.

We evaluated whether volatile anesthetics can improve the postoperative outcomes of non-cardiac surgery in patients with preoperative myocardial injury defined by the cardiac troponin elevation. From January 2010 to June 2018, 1254 adult patients with preoperative myocardial injury underwent non-cardiac surgery under general anesthesia and were enrolled in this study. Patients were stratified into following two groups according to anesthetic agents; 115 (9.2%) patients whose anesthesia was induced and maintained with continuous infusion of propofol and remifentanil (TIVA group) and 1139 (90.8%) patients whose anesthesia was maintainted with volatile anesthetics (VOLATILE group). The primary outcome was 30-day mortality. To diminish the remifentanil effect, a further analysis was conducted after excluding the patients who received only volatile anesthetics without remifentanil infusion. In a propensity-score matched analysis, 30-day mortality was higher in the TIVA group than the VOLATILE group (17.0% vs. 9.1%; hazard ratio [HR] 2.60; 95% confidence interval [CI], 1.14-5.93; p = 0.02). In addition, the TIVA group showed higher 30-day mortality than the VOLATILE group, even after eliminating the effect of remifentanil infusion (15.8% vs. 8.3%; HR 4.62; 95% CI, 1.82-11.74; p = 0.001). In our study, the use of volatile anesthetics showed the significant survival improvement after non-cardiac surgery in patients with preoperative myocardial injury, which appears to be irrelevant to the remifentanil use. Further studies are needed to confirm this beneficial effect of volatile anesthetics. Clinical trial number and registry URL: KCT0004349 (www.cris.nih.go.kr)., Competing Interests: NO authors have competing interests.

In perioperative settings where a patient under general anesthesia, presentation of serotonin syndrome might be far from the "classical" description of this potentially fatal condition. A patient who manifested signs of serotonin toxicity during an intravenous anesthetic, remifentanil, is presented. At the time of surgery, the patient was being treated with tramadol for pain management. The patient displayed myofasciculations on both gastrocnemius muscles confirmed electromyographically. All other conventional signs of serotonin syndrome were absent except hypotension and nystagmus. A presumptive diagnosis of serotonin syndrome was made intraoperatively. The symptoms resolved once remifentanil infusion was discontinued in the operating room without incident. Mild-to-moderate perioperative serotonin syndrome may manifest with myofasciculations in gastrocnemius muscles in the settings of no neuromuscular blockade. In spinal surgeries involving intraoperative EMG monitoring, the neuromonitoring team should be aware of this presentation and include serotonin syndrome in the differential diagnosis of unexplained EMG activity.

Objective: To investigate the curative effect of remifentanil on analgesia in newborns. Patients and methods: One hundred and twenty full-term puerperae from January 2013 to December 2013 were selected and randomly divided into three groups: remifentanil patient-controlled intravenous labor analgesia group (Group A, n  = 40), patient-controlled epidural analgesia (PCEA) group (Group B, n  = 40), and spontaneous labor group (Group C, n  = 40). General conditions, visual analogue scale (VAS) score, labor stage, bleeding, delivery mode, neonatal asphyxia rate, oxyhemoglobin saturation in puerpera, and umbilical arterial blood gas analysis indexes of the fetus were measured. In addition, complications and adverse reactions were recorded. Results: VAS scores in Group A and B were significantly lower than that in Group C at each time point after analgesic intervention ( p  < .05), without differences at 30 min and 1 h after analgesia between Group A and B ( p  > .05). However, VAS scores in Group A were significantly higher than those in Group B at the full opening of the uterine orifice and fetal delivery ( p  < .05). The active phases in the first stage of labor in Group A and B were significantly shorter than that in Group C ( p <.05). There were no significant differences in general conditions, VAS score before analgesia, the second and third stages of labor, delivery mode, bleeding, neonatal asphyxia rate, oxyhemoglobin saturation, pH value, partial pressure of oxygen (PO 2 ), and partial pressure of carbon dioxide (PCO 2 ) among three groups ( p  > .05). Conclusions: Remifentanil intravenous labor analgesia is not superior to PCEA, but does not increase adverse effects, suggesting it might be a supplementary method of PCEA.

Opiate addiction has risen substantially during the past decade. New treatments to combat opiate addiction are sorely needed. The current study was conducted to determine the acute individual and interactive effects of bupropion and dextromethorphan in a rat model of opiate self-administration using the short-acting synthetic opioid remifentanil. Both of these drugs have been found to reduce self-administration of nicotine. Bupropion and dextromethorphan and their combination had differential effects depending on whether the rats showed higher or lower baseline remifentanil self-administration. The rats with higher initial remifentanil self-administration showed a significant decrease in remifentanil self-administration with bupropion or dextromethorphan treatment, compared to the vehicle control condition. This decrease in self-remifentanil administration was most pronounced when combination of the higher doses of bupropion and dextromethorphan were administered. In contrast, the rats with lower baseline remifentanil self-administration showed the opposite effect of drug treatment with an increase in remifentanil self-administration with bupropion treatment compared to the vehicle control condition. Dextromethorphan had no significant effect inthis group. This study shows that combination bupropion and dextromethorphan affects remifentanil self-administration in a complex fashion with differential effects on low and high baseline responders. In subjects with high baseline remifentanil self-administration, bupropion and dextromethorphan treatment significantly reduced self-administration, whereas in subjects with low baseline remifentanil self-administration, bupropion increased remifentanil self-administration and dextromethorphan had no discernible effect. This finding suggests that combination bupropion-dextromethorphan should be tested in humans, with a focus on treating people with high-level opiate use., Competing Interests: Declaration of competing interest Dr. Davis receives research funding from Axsome Therapeutics, Inc. The other authors declare no conflicts of interest regarding the current research., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Rapid sequence induction (RSI) is recommended in patients at risk of aspiration, but induced haemodynamic adverse events, including tachycardia. In elderly patients, this trial aimed to assess the impact of the addition of remifentanil during RSI on the occurrence of: tachycardia (primary outcome), hypertension (due to intubation) nor hypotension (remifentanil)., Methods: In this three-arm parallel, double blind, multicentre controlled study, elderly patients (65 to 90 years old) hospitalised in three centres and requiring RSI were randomly allocated to three groups, where anaesthesia was induced with etomidate (0.3mg/kg) followed within 15seconds by either placebo, or low (0.5μg/kg), or high (1.0μg/kg) doses of remifentanil, followed by succinylcholine 1.0mg/kg. Heart rate (HR) and mean arterial pressure (MAP) were recorded before induction and after intubation., Results: In total, eighty patients were randomised and analysed. Baseline HR and MAP were similar between groups. For primary endpoint, the absolute change in HR between induction and intubation was greater in the control group (15 bpm; 95% CI [8-21]) than that in the remifentanil 0.5μg/kg group (4 bpm; 95% CI [-1-+8]; P=0.005) and the remifentanil 1.0μg/kg group (-3 bpm; 95% CI [-9-+3]; P<0.0001). The increase in MAP was greater in the placebo group than in both remifentanil groups (P<0.0001). Twice as many hypertension episodes were recorded in the placebo group compared to the remifentanil 0.5μg/kg and 1.0μg/kg groups (60%, 30%, and 28% patients respectively; P=0.032), but no placebo patients experienced hypotension episodes versus 11% and 24% in the remifentanil 0.5μg/kg and 1.0μg/kg groups respectively (P=0.016)., Conclusion: Remifentanil (0.5-1.0μg/kg) prevents the occurrence of tachycardia and hypertension in elderly patients requiring RSI., (Copyright © 2019. Published by Elsevier Masson SAS.)

Objective: To determine if acute opioid tolerance (AOT) or opioid-induced hyperalgesia (OIH) could develop and limit the remifentanil-induced reduction in the sevoflurane minimum alveolar concentration (MAC). The response to mechanical nociceptive threshold (MNT) was evaluated and related to OIH., Study Design: A crossover, randomized, experimental animal study., Animals: A total of nine Beagle dogs., Methods: The dogs were anaesthetized with sevoflurane in 50% oxygen. Baseline sevoflurane MAC was measured (MACb1). Remifentanil (0.3 μg kg -1 minute -1 ) or 0.9% saline constant rate infusion (CRI) was administered intravenously (IV). Sevoflurane MAC was determined 20 minutes after CRI was initiated (MACpostdrug1), 30 minutes after MACpostdrug1 determination (MACpostdrug2) and after 1 week (MACb2). The MNT was determined at baseline (before anaesthesia), 3 and 7 days after anaesthesia. An increase of MACpostdrug2 ≥0.25% compared to MACpostdrug1 was considered evidence of AOT. A decrease in MNT at 3 and 7 days or an increase in MACb2 or both with respect to MACb1 were considered evidence of OIH., Results: Remifentanil CRI reduced sevoflurane MACpostdrug1 by 43.7% with respect to MACb1. MACpostdrug2 was no different from MACpostdrug1 with the saline (p = 0.62) or remifentanil (p = 0.78) treatments. No significant differences were observed in the saline (p = 0.99) or remifentanil (p = 0.99) treatments between MACb1 and MACb2, or for MNT values between baseline, 3 and 7 days., Conclusion and Clinical Relevance: In dogs, under the study conditions, remifentanil efficacy in reducing sevoflurane MAC did not diminish in the short term, suggesting remifentanil did not induce AOT. Hyperalgesia was not detected 3 or 7 days after the administration of remifentanil. Contrary to data from humans and rodents, development of AOT or OIH in dogs is not supported by the findings of this study., (Copyright © 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

We aimed to evaluate the regulatory effects of propofol on high-dose remifentanil-induced hyperalgesia. A total of 180 patients receiving laparoscopic cholecystectomy were randomly divided into sevoflurane + high-dose remifentanil (SH) group, sevoflurane + low-dose remifentanil (SL) group and propofol + high-dose remifentanil group (PH) group (n=60). After intravenous administration of midazolam, SH and SL groups were induced with sevoflurane and remifentanil, and PH group was induced with propofol and remifentanil. During anesthesia maintenance, SH and SL groups were given 0.3 microg/kg/min and 0.1 microg/kg/min sevoflurane and remifentanil respectively, and PH group was given 0.3 microg/kg/min propofol and remifentanil. The three groups had significantly different awakening time, extubation time and total dose of remifentanil (P<0.001). Compared with SL group, periumbilical mechanical pain thresholds 6 h and 24 h after surgery significantly decreased in SH group (P<0.05), and the visual analog scale (VAS) scores significantly increased 30 min, 2 h and 6 h after surgery (P<0.05). Compared with SH group, periumbilical mechanical thresholds 6 h and 24 h after surgery were significantly higher in PH group (P<0.05), and VAS scores 30 min, 2 h and 6 h after surgery were significantly lower (P<0.05). PH group first used patient-controlled intravenous analgesia pump significantly later than SL group did (P<0.05). The total consumptions of sufentanil in PH and SL groups were significantly lower than that of SH group (P<0.05). The incidence rates of bradycardia and postoperative chill in PH and SH groups were significantly higher than those of SL group (P<0.05). Anesthesia by infusion of high-dose remifentanil plus sevoflurane caused postoperative hyperalgesia which was relieved through intravenous anesthesia with propofol.

Introduction: Type I thyroplasty, or medialization larygoplasty (ML), is a procedure which improves the voice by medializing a vocal fold with a permanent implant. Anesthetic management of these cases is challenging because patients can require periods of deep sedation followed by fully awake moments for phonation to assess the implant size. We present our experience of ML with or without arytenoid adduction (AA) using a multimodal anesthetic regimen consisting of concurrent infusions of dexmedetomidine, remifentanil, and propofol., Methods: This is a retrospective case series of patients anesthetized using this protocol from June 1, 2015 through June 30, 2017., Results: Seventy-five consecutive ML with or without AA patients anesthetized with dexmedetomidine and remifentanil infusions were identified, of which 74 (98.7%) also received concurrent propofol infusions. Mean duration of sedation was 190.9 ± 36.9 minutes and surgery was 139 ± 35.3 minutes. Transient hypopnea treated with supplemental oxygen complicated 18 (24%) cases and bradycardia requiring pharmacologic treatment complicated 3 (4%) cases. There were no other adverse anesthetic complications. One patient required surgical re-exploration due to postsurgical bleeding after the initial hospital discharge., Conclusion: In this cohort, a combination of remifentanil, dexmedetomidine and propofol infusions was well tolerated without serious adverse perioperative events., (Copyright © 2018. Published by Elsevier Inc.)

Remifentanil is commonly used clinically for perioperative pain relief, but it may induce postoperative hyperalgesia. Low doses of ketamine have remained a common choice in clinical practice, but the mechanisms of ketamine have not yet been fully elucidated. In this study, we examined the possible effects of ketamine on calcium/calmodulin-dependent protein kinase II α (CaMKIIα) and N-methyl-d-aspartate receptor (NMDAR) subunit NR2B in a mouse model of remifentanil-induced postoperative hyperalgesia (RIPH) in the primary somatosensory cerebral cortex (SI) region. The paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were used to assess mechanical allodynia and thermal hyperalgesia, respectively, before and after intraoperative remifentanil administration. Before surgery, mice received intrathecal injections of the following drugs: ketamine, NMDA, BayK8644 (CaMKII activator), and KN93 (CaMKII inhibitor). Immunofluorescence was performed to determine the anatomical location and expression of activated CaMKIIα, phosphorylated CaMKIIα (p-CaMKIIα). Additionally, western blotting was performed to assess p-CaMKIIα and NMDAR expression levels in the SI region. Remifentanil decreased the PWMT and PWTL at 0.5 h, 2 h, and 5 h and increased p-CaMKIIα expression in the SI region. Ketamine increased the PWMT and PWTL and reversed the p-CaMKIIα upregulation. Both BayK8644 and NMDA reversed the effect of ketamine, decreased the PWMT and PWTL, and upregulated p-CaMKIIα expression. In contrast, KN93 enhanced the effect of ketamine by reducing hyperalgesia and downregulating p-CaMKIIα expression. These results suggested that ketamine reversed RIPH by inhibiting the phosphorylation of CaMKIIα and the NMDA receptor in the SI region in mice., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Unsatisfactory analgesia would occur frequently during repeated cesarean section under epidural anesthesia. The aim of this study is to observe the effects of intravenous remifentanil on maternal comfort, maternal and neonatal safety during repeated cesarean section under epidural anesthesia., Methods: A total of 80 parturients undergoing repeated cesarean section were involved in the study. The patients were randomly divided into the intravenous remifentanil- assisted epidural group (group R) and epidural group (group E), respectively (n = 40). In group R, the remifentanil was continuously intravenously infused as an adjuvant to epidural anesthesia. In group E, 0.75% ropivacaine epidural or intravenous ketamine was administered as needed. Parturient baseline characteristics, vital signs, VAS scores, and comfort scores during surgery were recorded. Adverse effects were also recorded., Results: A total of 80 patients were enrolled in the current study and the final analyses included 39 patients in group R and 38 patients in group E. No differences in patients' baseline characteristics were found between the two groups (p > 0.05). Compared with group E, the comfort score was significantly higher in group R (9.1 ± 1.0 vs. 7.5 ± 1.3, p <  0.001), whereas the maximum VAS score was significantly lower in group R (1.8 ± 1.2 vs. 4.1 ± 1.0, p <  0.001). Maternal and neonatal adverse effects did not differ between the two groups during surgery (p > 0.05)., Conclusions: Continuous intravenous infusion of low-dose remifentanil can significantly improve the experience of parturients undergoing repeated cesarean section under epidural anesthesia, without noticeable maternal or neonatal adverse effects., Trial Registration: This study was pre-registered at http://www.chictr.org.cn/index.aspx (ChiCTR1800018423) on 17/09/2018.

Objectives: To explore women's experiences of remifentanil or pethidine for labour pain and infant feeding behaviours at 6weeks post partum., Design: Qualitative postnatal sub-study to the randomised controlled trial of remifentanil intravenous patient controlled analgesia (PCA) versus intramuscular pethidine for pain relief in labour (RESPITE). Semistructured telephone interviews were conducted at 6 weeks post partum, and thematic analysis was undertaken., Setting: Women recruited to the RESPITE trial from seven UK hospitals., Participants: Eighty women consented and 49 (30 remifentanil group and 19 pethidine group) completed the interview., Results: Eight themes emerged which encompassed women's antenatal plans for pain management ( Birth Expectations ) through to their future preferences for pain relief ( Reflections for Future Choices ). Many women who used remifentanil felt it provided effective pain relief ( Effectiveness of Pain Relief ), whereas women in the pethidine group expressed more mixed views. Both groups described side effects, with women using pethidine frequently reporting nausea ( Negative Physiological Responses ) and women using remifentanil describing more cognitive effects ( Cognitive Effects ). Some women who used remifentanil reported restricted movements due to technical aspects of drug administration and fear of analgesia running out ( Issues with Drug Administration ). Women described how remifentanil enabled them to maintain their ability to stay focused during the birth ( Enabling a Sense of Control ). There was little difference in reported breastfeeding initiation and continuation between pethidine and remifentanil groups ( Impact on Infant Behaviour and Breastfeeding )., Conclusions: Qualitative insights from a follow-up study to a trial which explored experiences of intravenous remifentanil PCA with intramuscular pethidine injection found that remifentanil appeared to provide effective pain relief while allowing women to remain alert and focused during labour, although as with pethidine, some side effects were noted. Overall, there was little difference in reported breastfeeding initiation and duration between the two groups., Trial Registration Number: ISRCTN29654603., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Opioids are the most powerful analgesics available to date. However, they may also induce adverse effects including paradoxical opioid-induced hyperalgesia. A mechanism that might underlie opioid-induced hyperalgesia is the amplification of synaptic strength at spinal C-fibre synapses after withdrawal from systemic opioids such as remifentanil ("opioid-withdrawal long-term potentiation [LTP]"). Here, we show that both the induction as well as the maintenance of opioid-withdrawal LTP were abolished by pharmacological blockade of spinal glial cells. By contrast, the blockade of TLR4 had no effect on the induction of opioid-withdrawal LTP. D-serine, which may be released upon glial cell activation, was necessary for withdrawal LTP. D-serine is the dominant coagonist for neuronal NMDA receptors, which are required for the amplification of synaptic strength on remifentanil withdrawal. Unexpectedly, opioid-withdrawal LTP was transferable through the cerebrospinal fluid between animals. This suggests that glial-cell-derived mediators accumulate in the extracellular space and reach the cerebrospinal fluid at biologically active concentrations, thereby creating a soluble memory trace that is transferable to another animal ("transfer LTP"). When we enzymatically degraded D-serine in the superfusate, LTP could no longer be transferred. Transfer LTP was insensitive to pharmacological blockade of glial cells in the recipient animal, thus representing a rare form of glial cell-independent LTP in the spinal cord.

Background: Dexmedetomidine is a sedative with modest analgesic efficacy, whereas remifentanil is an opioid analgesic with modest sedative potency. Synergy is often observed when sedative-hypnotics are combined with opioid analgesics in anesthetic practice. A three-phase crossover trial was conducted to study the pharmacodynamic interaction between remifentanil and dexmedetomidine., Methods: After institutional review board approval, 30 age- and sex- stratified healthy volunteers were studied. The subjects received consecutive stepwise increasing target-controlled infusions of dexmedetomidine, remifentanil, and remifentanil with a fixed dexmedetomidine background concentration. Drug effects were measured using binary (yes or no) endpoints: no response to calling the subject by name, tolerance of shaking the patient while shouting the name ("shake and shout"), tolerance of deep trapezius squeeze, and tolerance of laryngoscopy. The drug effect was measured using the electroencephalogram-derived "Patient State Index." Pharmacokinetic-pharmacodynamic modeling related the administered dexmedetomidine and remifentanil concentration to these observed effects., Results: The binary endpoints were correlated with dexmedetomidine concentrations, with increasing concentrations required for increasing stimulus intensity. Estimated model parameters for the dexmedetomidine EC50 were 2.1 [90% CI, 1.6 to 2.8], 9.2 [6.8 to 13], 24 [16 to 35], and 35 [23 to 56] ng/ml, respectively. Age was inversely correlated with dexmedetomidine EC50 for all four stimuli. Adding remifentanil did not increase the probability of tolerance of any of the stimuli. The cerebral drug effect as measured by the Patient State Index was best described by the Hierarchical interaction model with an estimated dexmedetomidine EC50 of 0.49 [0.20 to 0.99] ng/ml and remifentanil EC50 of 1.6 [0.87 to 2.7] ng/ml., Conclusions: Low dexmedetomidine concentrations (EC50 of 0.49 ng/ml) are required to induce sedation as measured by the Patient State Index. Sensitivity to dexmedetomidine increases with age. Despite falling asleep, the majority of subjects remained arousable by calling the subject's name, "shake and shout," or a trapezius squeeze, even when reaching supraclinical concentrations. Adding remifentanil does not alter the likelihood of response to graded stimuli.

Background: During labour, remifentanil patient-controlled analgesia is used as an alternative to neuraxial analgesia. Remifentanil is associated with hypoventilation and respiratory depression but the frequency of serious maternal and neonatal adverse events is unknown. The aim of this study was to estimate the number of serious adverse events attributed to the use of remifentanil patient-controlled analgesia during labour in The Netherlands and to investigate the circumstances (e.g. monitoring, practice deviations) of these events and the subsequent management., Methods: In a nationwide survey among obstetricians, anaesthetists and clinical midwives the frequency of serious adverse events was assessed. A questionnaire was sent by email to all 61 Dutch hospitals in which remifentanil patient-controlled analgesia is, or has been, available for labour analgesia. All reported cases were assessed independently by two expert teams., Results: We received information from all hospitals. After independent assessments, 17 cases of single maternal desaturation; 10 maternal cases of apnoea, bradycardia and/or cardiac arrest; and two neonatal cases of respiratory depression, over a period of more than 10 years of remifentanil patient-controlled analgesia use, were identified as a serious adverse event. All serious adverse events were resolved without irreversible damage., Conclusions: The risk of a potentially life-threatening serious adverse event attributed to remifentanil patient-controlled analgesia seems to be low. All patients recovered without deficit. Adherence to strict monitoring and the attendance of trained healthcare providers is required to safely use remifentanil for labour analgesia., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Central venous catheter (CVC) insertion is a common practice for anesthetists, but this invasive procedure generates anxiety and pain in patients that are often underestimated. We compared target-controlled infusion of remifentanil and local lidocaine infiltration with placebo and local lidocaine infiltration to decrease pain scores during CVC placement., Materials and Methods: We included conscious, adult patients without contraindication to remifentanil or lidocaine. We excluded pregnant women, emergency situations, and opioid abuse. Patients requiring CVC were randomly assigned, using computer-generated allocation numbers stored in sealed envelopes, to receive target-controlled infusion of remifentanil or placebo-all patients received local anesthesia with lidocaine. All patients were hospitalized in a recovery room or intensive care unit, monitored, and received 4 L/min of oxygen.The primary outcome was global pain (Verbal Numeric Rating Pain Scale) during the procedure. Secondary outcomes were pain perceived at every stage of the procedure, anxiety, patient satisfaction, operational ease, and side effects., Results: In this double-blind study, we included 90 patients (split into 2 groups of 45 patients). Global pain was significantly reduced in the remifentanil group: 20 of 100 (95% confidence interval, 16-40) versus 50 of 100 (95% confidence interval, 40-60) in the placebo group; P=0.0009. No major adverse events were observed during this study, and there were no significant differences between both groups regarding side effects., Discussion: Target-controlled infusion of remifentanil is an effective drug to reduce pain during CVC insertion in association with lidocaine-based local anesthesia, in conscious patients.