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      Effects of different sufentanil target concentrations on the MAC BAR of sevoflurane in patients with carbon dioxide pneumoperitoneum stimulus

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          Abstract

          Background

          This study aims to observe the effects of different target controlled plasma sufentanil concentrations on the minimum alveolar concentration (MAC) of sevoflurane for blocking adrenergic response (BAR) in patients undergoing laparoscopic cholecystectomy with carbon dioxide pneumoperitoneum stimulation.

          Methods

          Eighty-five patients undergoing laparoscopic cholecystectomy, aged 30–65 years, with American Society of Anesthesiologists physical status I-II, were enrolled in this study. All the patients were randomly divided into 5 groups (S 0, S 1, S 2, S 3, S 4) with different sufentanil plasma target concentration (0.0, 0.1, 0.3, 0.5, 0.7 ng ml − 1). Anesthesia was induced by inhalation of 8% sevoflurane in 100% oxygen, and 0.6 mg kg − 1 of rocuronium was intravenously injected to facilitate the insertion of a laryngeal mask airway. The end-tidal sevoflurane concentration and sufentanil plasma target concentration were adjusted according to respective preset value in each group. The hemodynamic response to pneumoperitoneum stimulus was observed after the end-tidal sevoflurane concentration had been maintained stable at least for 15 min. The MAC BAR of sevoflurane was measured by a sequential method. Meanwhile, epinephrine (E) and norepinephrine (NE) concentrations in the blood were also determined before and after pneumoperitoneum stimulus in each group.

          Results

          When the method of independent paired reversals was used, the MAC BAR of sevoflurane in groups S 0, S 1, S 2, S 3, S 4 was 5.333% (confidence interval [CI] 95%: 5.197–5.469%), 4.533% (95% CI: 4.451–4.616%), 2.861% (95% CI: 2.752–2.981%), 2.233% (95% CI: 2.142–2.324%) and 2.139% (95% CI: 2.057–2.219%), respectively. Meanwhile, when the isotonic regression analysis was used, the MAC BAR of sevoflurane in groups S 0, S 1, S 2, S 3, S 4 was 5.329% (95% CI: 5.321–5.343%), 4.557% (95% CI: 4.552–4.568%), 2.900% (95% CI: 2.894–2.911%), 2.216% (95% CI: 2.173–2.223%) and 2.171% (95% CI: 2.165–2.183%), respectively. The MAC BAR was not significantly different between groups S 3 and S 4 when using 0.5 and 0.7 ng ml − 1 of sufentanil plasma target concentrations. No significant difference was found in the change of E or NE concentration between before and after pneumoperitoneum stimulation in each group.

          Conclusions

          The MAC BAR of sevoflurane can be decreased with increasing sufentanil plasma target concentrations. A ceiling effect of the decrease occurred at a sufentanil plasma target concentration of 0.5 ng ml − 1. When the sympathetic adrenergic response was inhibited in half of the patients to pneumoperitoneum stimulation in each group, the changes of E and NE concentrations showed no significant differences.

          Trial registration

          The study was registered at http://www.chictr.org.cn ( ChiCTR1800015819, 23, April, 2018).

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          Most cited references29

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          Staircase bioassay: The up-and-down method

          W.J. Dixon (1991)
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            Advances in understanding the actions of nitrous oxide.

            Nitrous oxide (N(2)O) has been used for well over 150 years in clinical dentistry for its analgesic and anxiolytic properties. This small and simple inorganic chemical molecule has indisputable effects of analgesia, anxiolysis, and anesthesia that are of great clinical interest. Recent studies have helped to clarify the analgesic mechanisms of N(2)O, but the mechanisms involved in its anxiolytic and anesthetic actions remain less clear. Findings to date indicate that the analgesic effect of N(2)O is opioid in nature, and, like morphine, may involve a myriad of neuromodulators in the spinal cord. The anxiolytic effect of N(2)O, on the other hand, resembles that of benzodiazepines and may be initiated at selected subunits of the gamma-aminobutyric acid type A (GABA(A)) receptor. Similarly, the anesthetic effect of N(2)O may involve actions at GABA(A) receptors and possibly at N-methyl-D-aspartate receptors as well. This article reviews the latest information on the proposed modes of action for these clinical effects of N(2)O.
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              [3H]Sufentanil, a superior ligand for mu-opiate receptors: binding properties and regional distribution in rat brain and spinal cord.

              Stereospecific [3H]sufentanil binding, inhibited by dextromoramide, represents 90% of the total binding in membrane preparations of rat brain and spinal cord. Scatchard plots of the binding in the forebrain, at 37 degrees C in Tris-HCl buffer without and with 120 mM NaCl, were rectilinear; KD = 0.13 nM and 0.31 nM, Bmax = 13 fmol/mg tissue and 9.9 fmol/mg tissue in the absence and the presence of sodium ions respectively. The reduction in binding affinity in the presence of sodium ions was found to be due to a 9.7 fold enhancement of the initial dissociation rate from t1/2 = 2.1 min in the absence to 13 s in the presence of sodium ions. The [3H]sufentanil binding properties were superior to those of [3H]fentanyl, [3H]dihydromorphine and [3H]naloxone; [3H]sufentanil showed an unmatched favourable ratio of stereospecific versus non-specific binding; it had a 7.7, 20 and 40 fold binding affinity than the above ligands respectively. Due to its relatively slow dissociation rate, a more accurate estimation of the Bmax value was obtained with [3H]sufentanil than with the other, fast dissociating 3H-ligands (t1/2 less than 10 s). A total of 37 narcotic analgesic agonists and antagonists belonging to 5 different major structural classes all inhibited stereospecific [3H]sufentanil binding in a competitive way. There was no relationship between binding affinities and lipophilicity and degree of ionization of the compounds. Binding affinities correlated highly significantly with the analgesic potency measured in vivo, demonstrating that [3H]sufentanil labels mu-opiate receptor sites which mediate narcotic analgesia. Moreover, the binding affinity of sufentanil for delta-type binding sites labelled by [3H] [D-Ala2,D-Leu5]enkephalin was found to be 100 times lower than its binding affinity for the mu-receptor sites. [3H]Sufentanil was used for a detailed investigation of the regional distribution of mu-opiate receptor sites in the brain; Bmax and KD values were measured in the dorsal and ventral spinal cord.
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                Author and article information

                Contributors
                879921874@qq.com
                Journal
                BMC Anesthesiol
                BMC Anesthesiol
                BMC Anesthesiology
                BioMed Central (London )
                1471-2253
                21 September 2020
                21 September 2020
                2020
                : 20
                : 239
                Affiliations
                [1 ]GRID grid.413387.a, ISNI 0000 0004 1758 177X, Department of Anaesthesiology, , Affiliated Hospital of North Sichuan Medical College, ; Nanchong, 637000 Sichuan China
                [2 ]GRID grid.413387.a, ISNI 0000 0004 1758 177X, Department of Clinical Laboratory, , Affiliated Hospital of North Sichuan Medical College, ; Nanchong, 637000 Sichuan China
                Author information
                http://orcid.org/0000-0003-0986-8001
                Article
                1160
                10.1186/s12871-020-01160-1
                7504852
                8f2dbfb6-771a-4d17-afcd-0c0430f05093
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 3 May 2020
                : 15 September 2020
                Funding
                Funded by: Institution of Medicine of Sichuan Province
                Award ID: no. S15025
                Funded by: Nanchong science and technology bureau
                Award ID: no. 18SXHZ0161
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Anesthesiology & Pain management
                anesthetics, inhalation,sufentanil,pneumoperitoneum
                Anesthesiology & Pain management
                anesthetics, inhalation, sufentanil, pneumoperitoneum

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