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      Dezocine prevents sufentanil-induced cough during general anesthesia induction: a meta-analysis of randomised controlled trials

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          Abstract

          Background

          Sufentanil is one of the opioids currently used to induce general anesthesia, and cough is one of the most common complications. Many drugs have been used to prevent sufentanil-induced cough (SIC), and dezocine is one of them. Dezocine is an analgesic, acting as partial antagonist of κ-receptors and agonist of μ-receptors. The purpose of our meta-analysis is to evaluate the efficacy of dezocine on SIC.

          Methods

          We searched multiple databases including PubMed, Embase, ScienceDirect, the Cochrane Library, and China National Knowledge Infrastructure databases (CNKI) to identify studies that met the inclusion criteria. This meta-analysis focused on the incidence and severity of SIC after dezocine intervention, as well as adverse effects. This meta-analysis was registered on PROSPERO with reference number ID: CRD 42020144943.

          Results

          Five randomised controlled trials (RCTs) were identified, including 890 patients. Each study was a comparison of dezocine with an equal volume of 0.9% saline. When the injection dose of dezocine was 0.1 mg/kg, the incidence (pooled risk ratio (RR) = 0.03, [95% CI: 0.02 to 0.07], P < 0.00001, I 2  = 0%) and severity (mild: RR = 0.07, [95% CI: 0.03 to 0.18], P < 0.00001, I 2  = 0%; moderate: RR = 0.05, [95% CI: 0.02 to 0.16], P < 0.00001, I 2  = 0%; severe: RR = 0.04, [95% CI: 0.01 to 0.16], P < 0.00001, I 2  = 0%) of SIC were significantly decreased. There were no statistically significant differences in vital signs between the two groups based on the results of the pooled analysis.

          Conclusion

          This meta-analysis showed that dezocine significantly reduced the incidence and severity of SIC in the induction of general anesthesia, but had no significant effect on vital signs. More high-quality RCTs are needed to complement existing conclusions.

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          Most cited references25

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          Novel molecular targets of dezocine and their clinical implications.

          Although dezocine is a partial μ-opioid receptor agonist, it is not a controlled substance. Thus, the characterization of the molecular targets of dezocine is critical for scientific and clinical implications. The goal of this study is to characterize molecular targets for dezocine and determine their implications. A binding screen for dezocine was performed on 44 available receptors and transporter proteins. Functional assays for the novel targets were performed along with computation calculations to locate the binding site. A G protein activation study was performed for the human κ opioid receptor to determine whether dezocine is a κ-antagonist. Data are presented as mean ± standard error. The affinities for dezocine were 3.7 ± 0.7 nM for the μ receptor, 527 ± 70 nM for the δ-receptor, and 31.9 ± 1.9 nM for the κ-receptor. Dezocine failed to induce G protein activation with κ-opioid receptor and concentration dependently inhibited κ-agonist (salvinorin A and nalbuphine)-induced receptor activation, indicating that dezocine is a κ-antagonist. Two novel molecular targets (norepinephrine transporter and serotonin transporter) were identified. Dezocine concentration-dependently inhibited norepinephrine and serotonin reuptake in vitro. The half maximal inhibitory concentrations (expressed as pIC50) were 5.68 ± 0.11 for norepinephrine transporter and 5.86 ± 0.17 for serotonin transporter. Dezocine occupied the binding site for known norepinephrine transporter and serotonin transporter inhibitors. The unique molecular pharmacological profile of dezocine as a partial μ-receptor agonist, a κ-receptor antagonist, and a norepinephrine and serotonin reuptake inhibitor (via norepinephrine transporter and serotonin transporter) was revealed. These discoveries reveal potentially important novel clinical implications and drug interactions of dezocine.
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            Intravenous lidocaine and ephedrine, but not propofol, suppress fentanyl-induced cough.

            The aim of this study was to evaluate the effectiveness of lidocaine, propofol and ephedrine in suppressing fentanyl-induced cough. One hundred and eighteen patients were randomly assigned into four groups and the following medications were given intravenously: patients in Group I (n = 31) received normal saline 2 mL, Group II (n = 29) received lidocaine 2 mg.kg(-1), Group III (n = 30) received propofol 0.6 mg.kg(-1) and Group IV (n = 28) received ephedrine 5 mg. At one minute after the study medication, fentanyl 2.5 microg.kg(-1) was given intravenously within two seconds. The occurrence of cough and vital sign profiles were recorded within two minutes after fentanyl bolus by an anesthesiologist blinded to study design. Sixty-five percent of patients in the placebo group had cough, whereas the frequency was significantly decreased in Groups II (14%) and IV (21%). Although a numerically lower frequency of cough was noted in Group III (37%), it was not statistically different from that of the placebo group. SpO(2) decreased significantly in patients of Group III compared to placebo; one patient experienced hypoxemia necessitating mask ventilation. Patients in Group III showed a decrease in heart rate and systolic blood pressure (2 beats.min(-1) and 8 mmHg vs baseline). Patients in Group IV showed an increase in both measurements (5 beats.min(-1) and 8 mmHg vs baseline). No truncal rigidity was observed throughout the study. Intravenous lidocaine 2 mg.kg(-1) or ephedrine 5 mg, but not propofol 0.6 mg.kg(-1), was effective in preventing fentanyl-induced cough. The results provide a convenient method to decrease fentanyl-induced cough.
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              Salbutamol, beclomethasone or sodium chromoglycate suppress coughing induced by iv fentanyl.

              Fentanyl, a synthetic opioid, is a popular choice amongst anesthesiologists in the operating room. Preinduction iv fentanyl bolus is associated with coughing in 28-45% of patients. Coughing due to fentanyl is not always benign and at times may be explosive requiring immediate intervention. We have studied the role of aerosol inhalation of salbutamol, beclomethasone and sodium chromoglycate in preventing fentanyl induced coughing and have compared their efficacy. Two hundred patients aged 18-60 yr, undergoing elective laparoscopic cholecystectomy were randomized into four groups of 50 each. Group I served as control, while Groups II, III and IV received an aerosol inhalation of salbutamol, beclomethasone or sodium chromoglycate 15 min prior to entering the operating room. Following iv fentanyl (2 micro g x kg(-1)) the incidence of cough was recorded and graded as mild (1-2), moderate (3-5) and severe (> 5) depending on the number of coughs observed. Results were analyzed using 'z' and Fischer's Exact test. A P value of /= 0.05). The use of salbutamol, beclomethasone or sodium chromoglycate aerosol 15 min prior to iv fentanyl administration minimizes fentanyl-induced coughing.
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                Author and article information

                Contributors
                xiongzc0527@163.com
                13811758985@139.com
                bxhno1@163.com
                zrtanms@163.com
                Journal
                BMC Anesthesiol
                BMC Anesthesiol
                BMC Anesthesiology
                BioMed Central (London )
                1471-2253
                22 June 2020
                22 June 2020
                2020
                : 20
                : 154
                Affiliations
                [1 ]GRID grid.506261.6, ISNI 0000 0001 0706 7839, Graduate School of Peking Union Medical College, , Chinese Academy of Medical Sciences, ; Beijing, 100730 People’s Republic of China
                [2 ]GRID grid.415954.8, ISNI 0000 0004 1771 3349, Department of Spine Surgery, , China-Japan Friendship Hospital, ; No. 2 Yinghua Dongjie, Hepingli, Chaoyang District, Beijing, 100029 People’s Republic of China
                Author information
                http://orcid.org/0000-0002-0511-9735
                Article
                1076
                10.1186/s12871-020-01076-w
                7310133
                549ba3c1-7b52-4ee3-abea-e32b823cb4ef
                © 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
                : 25 October 2019
                : 18 June 2020
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Anesthesiology & Pain management
                dezocine,sufentanil,cough,general anesthesia,randomised controlled trials

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