Comparative Study Of Sevoflurane And Propofol During Acute Respiratory Distress Syndrome Supported With ECMO

Part Ⅰ Bibliometric Analysis of sedation management in extracorporeal membrane oxygenationObjective To explore the current research status,development trend and hotspots of sedation management in extracorporeal membrane oxygenation(ECMO).Methods To conduct bibliometric analysis related to sedation management of ECMO in PubMed and Web of Science core set databases from the aspects of discipline distribution,institutional cooperation,author distribution and keyword analysis by using Citespace 5.7.R1 software and Microsoft Excel 2019 software.Results At present,the subjects that pay most attention to this field are general internal medicine and anesthesiology.The affiliated hospitals of colleges are relatively more active in this field.Academic teams led by Daniel Brodie,Kiran Shekar,Antonio Pesenti,Elena Spinelli,Tommaso Mauri,and others have been formed,among which Daniel Brodie has the most fruitful achievements.The keywords with the highest frequency are "extracorporeal membrane oxygenation","children","management strategy","respiratory distress syndrome","pharmacokinetics",and so on.Conclusion At the present stage,research is mainly concentrated in general internal medicine and anesthesiology,and shows the development of multi-discipline cooperation.The affiliated institutions of colleges have the most important influence on scientific research innovation,but the academic communication is still weak.The current research hotspots are mainly focused on sedation management of infants and children receiving ECMO,the prognosis of patients under different sedation management,sedation strategies for patients with acute respiratory distress syndrome,cardiogenic shock or other different diseases,as well as changes in physiological metabolism,pharmacokinetics and pharmacodynamics related to ECMO.Part Ⅱ Inflammatory cytokine of sevoflurane versus propofol during mechanical ventilation:a meta-analysis based on a randomized controlled studyBackground:During general anesthesia,ventilators are required to assist mechanical ventilation to maintain oxygenation and the stability of the acid-base balance in the internal environment.Although mechanical ventilation can help patients maintain the stability of oxygenation during surgery,surgical procedures and mechanical ventilation can also cause systemic or local inflammatory reactions at the same time.Ventilator-associated acute lung injury,postoperative pneumonia,atelectasis and other complications and the control of inflammation are closely related to the prognosis and mortality of patients,especially due to mechanical ventilation.Sevoflurane and propofol are the most commonly used narcotic drugs for intraoperative anesthesia maintenance.Sevoflurane is an inhaled narcotic drug,which mainly acts through alveolar absorption,while propofol is administered intravenously to maintain anesthesia.Some studies have found that both of them have certain anti-inflammatory effects and can reduce inflammation.However,there is still controversy about the effect of the two drugs on inflammation in clinical practice.Objective:The effect of sevoflurane and propofol on systemic and local lung inflammation during operation is still controversial.Through Meta-analysis,the data of the currently published randomized controlled studies of sevoflurane and propofol on systemic and local lung inflammation were combined to evaluate the effects of the two narcotic drugs on systemic and pulmonary inflammation,so as to provide a theoretical reference for clinical practice.Method:Through the VIP,Wanfang database,Chinese Biomedical Literature Database(CBM),China National Knowledge Infrastructure(CNKI)database and four English databases of The Cochrane Library,EMBASE,PubMed and Web of Science were searched for randomized controlled studies on the effects of sevoflurane and propofol on systemic or local lung inflammation.According to the pre-set inclusion and exclusion criteria,the literatures that met the purpose of the study were screened out.JADAD scale was used to evaluate the quality of the included studies.RevMan5.3 statistical analysis software was used for data synthesis of meta-analysis.The main outcome measures included the levels of interleukin-6,interleukin-8,and interleukin-10 in alveolar lavage fluid,and the levels of interleukin-6,interleukin-8,interleukin-10,and tumor necrosis factor-α in serum.Results:A total of 26 randomized controlled studies were included in this study,including 14 foreign literatures and 12 Chinese literatures.A total of 1714 patients from 9 countries were included,including 858 patients in the sevoflurane group and 856 patients in the propofol group.There was no statistical difference in baseline data between the two groups.There is no significant difference in alveolar lavage fluid interleukin-6(Weighted mean difference:-0.19,95%CI:-0.81-0.43,P=0.55),interleukin-8(weighted mean difference:-83,95%CI:-231.92-65.92,P=0.27),interleukin-10(weighted mean difference:-83.54,95%CI:-274.66-107.58,P=0.39)and tumor necrosis factor-α(weighted mean difference:-2.98,95%CI:-6.93-0.98,P=0.14).In sevoflurane group,serum pro-inflammatory factors interleukin-6(weighted mean difference:4.11,95%CI:0.78-7.45,P=0.02)and interleukin-8(weighted mean difference:16.11,95%CI:6.15-26.06,P=0.002)was significantly higher than that in the propofol group.However,the level of interleukin-10 which act as anti-inflammatory cytokine was higher in the sevoflurane group(weighted mean difference:-3.94,95%CI:-6.02,-1.86,P=0.0002).And there is no significant difference in serum tumor necrosis factor-α(weighted mean difference:-0.36,95%CI:-1.85-1.12,P=0.63)between two groups.Conclusion:The proinflammatory factors IL-6 and IL-8 in serum were significantly lower in the sevoflurane group compared with propofol group.What’s more,IL-10 which act as anti-inflammatory cytokine was significantly higher in the sevoflurane group.Compared with propofol,sevoflurane has a better effect on reducing and inhibiting inflammation during general anesthesia surgery.In the future,more randomized controlled studies with large samples are needed to confirm these conclusions.Part Ⅲ Study on the protection mechanism of sevoflurane against ARDS based on network pharmacology strategyBackground:Acute respiratory distress syndrome(ARDS)is a common critical disease in ICU.Venous extracorporeal membrane oxygenation(VV ECMO)is currently considered to be a reasonable choice for the treatment of ARDS.Network pharmacology has become a powerful means to understand the mechanism of drugs in disease treatment.Objective:The purpose of this study was to compare the effects of sevoflurane and propofol in VV ECMO assisted acute respiratory distress syndrome,and to explore the protective mechanism of sevoflurane on ARDS from the perspective of network pharmacology.Method:In the aspect of in vivo experimental verification,this study used oleic acid to induce the rat ARDS model,and on the basis of this model,a special 5.5Fr three chamber tube was placed through the right internal jugular vein(the distal end of the 20G tube was the drainage end of the vein,the middle part of the 22G tube was the infusion channel,and the proximal end of the 22G tube was the perfusion end of the vein)to establish the rat VV ECMO model.To explore the role of sevoflurane and propofol in VV ECMO assisted ARDS model in rats,the experiment was divided into three groups:control group(Con group),sevoflurane group(Sev group)and propofol group(Pro group),with 5 rats in each group.The auxiliary time of VV ECMO is 3 hours,during which vital signs are monitored in real time,and blood gas is detected at TO(baseline),T1(ARDS modeling time)and T3(after VV ECMO support).The lung wet/dry ratio was used to measure the severity of pulmonary edema.Hematoxylin eosin staining and immunohistochemical techniques reflect the pathological changes of lung tissue.The expression of inflammatory factors was detected by enzyme-linked immunosorbent assay.Use the Pubchem database(https://pubchem.ncbi.nlm.nih.gov/)search for potential targets of sevoflurane and use GeneCardard human gene database and DisGenet database(https://www.disgenet.org/)OMIM database(https://omim.org/)and CTD database(http://ctdbase.org/)Retrieve acquired disease targets of ARDS.Through cross analysis of potential therapeutic targets of sevoflurane and disease targets of ARDS,common targets were obtained and constructed into PPI(protein protein interaction)network diagram of sevoflurane RDS.Through DAVID Bioinformation Resources 6.8(https://david.ncifcrf.gov/home.jsp)the database has rich functions.Finally,the above results were analyzed and verified by molecular docking technology.Results:In vivo experiment showed that the partial pressure of blood oxygen(PaO2),oxygenation index(PaO2/FiO2),and mean arterial pressure(MAP)of Sev group in T1 phase were lower than those in T0 phase(P<0.05).In Sev group,PaO2,PaO2/FiO2 and MAP in T3 phase were significantly higher than those in T2 phase(P<0.05).The pathological changes in Pro group were mild interstitial hyperplasia,moderate vascular congestion,and moderate inflammatory cell infiltration.The above pathological changes in Sev group were obviously alleviated.The lung Wet/Dry ratio reflected the change of pulmonary edema.The lung Wet/Dry ratio in the Sev group was lower than that in the Pro group,with a statistically significant difference(P<0.05).The protein concentration in alveolar lavage fluid was measured.The results showed that pulmonary capillary leakage in Sev group was significantly reduced compared with that in Pro group(P<0.05).In terms of inflammatory factors,the expression levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in lung tissue,alveolar lavage fluid and serum of rats in Sev group were significantly lower than those in Pro group(P<0.05).The above experimental results show that sevoflurane sedation can improve the lung function and reduce inflammatory reaction when VV ECMO assists ARDS.Therefore,we will further explore the protective mechanism of sevoflurane on ARDS from the perspective of network pharmacology.In target screening,184 sevoflurane therapeutic targets and 3786 ARDS related target genes were found,and 69 common targets were obtained.PPI network diagram describes the relationship and role of CEP and ARDS related genes.The network consists of 69 nodes and 436 edges.In the enrichment analysis results,359 entries are rich in gene ontology,including 36 cell components(CC),255 biological processes(BP)and 68 molecular functions(MF).The enrichment of KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway mainly involves cancer pathway,prostate cancer pathway EGFR tyrosine kinase inhibitor resistance,PI3K-Akt signal pathway,prolactin signal pathway,ErbB signal pathway,lipid and atherosclerosis,estrogen signal pathway,etc.The results of molecular docking showed that sevoflurane had good binding activity.Conclusion:In this study,a rat model of ARDS assisted by VV ECMO was established,and sevoflurane and propofol were used for sedation during the assisted period.The experimental results showed that sevoflurane,compared with propofol,had obvious anti-inflammatory and pulmonary function improvement effects,which was confirmed in the network pharmacological results,laying a theoretical foundation for the clinical application of sevoflurane in VV ECMO assisted ARDS.