Application Of Non Tracheal Intubation And Autonomic Breathing Anesthesia In Video-assisted Thoracic Surgery

Part 1:Non-intubated anesthesia in patients undergoing video-assisted thoracoscopic surgery:A systematic review and meta-analysisObjective:Non-intubated anesthesia（NIA）has been proposed for video-assisted thoracoscopic surgery（VATS）,although how the benefit-to-risk of NIA compares to that of intubated general anesthesia（IGA）for certain types of patients remains unclear.Therefore,the aim of the present meta-analysis was to understand whether NIA or IGA may be more beneficial for patients undergoing VATS.Methods:A systematic search of Cochrane Library,Pubmed and Embase databases from January 1968 to April 2019 was performed using predefined criteria.Studies comparing the effects of NIA or IGA for adult VATS patients were considered.According to Cochrane system evaluator’s manual（5.1.0version）,the quality evaluation and data extraction of the included studies were carried out,and the meta analysis was carried out by using stata14.0 statistical software.Pooled data were meta-analyzed using a random-effects model to determine the standard mean difference（SMD）with 95%confidence intervals（CI）.The primary outcome measure was hospital stay,and the secondary outcome measures were the cost of stay,the duration of thoracic drainage tube,the time of eating and the immune inflammatory response.Results:Twenty-eight studies with 2929 patients were included.The median age of participants was 56.8 years（range 21.9–76.4）and 1802（61.5%）were male.Compared to IGA,NIA was associated with shorter hospital stay（SMD-0.57 days,95%CI-0.78 to-0.36）,lower estimated cost for hospitalization（SMD-2.83 US,95%CI-4.33 to-1.34）,shorter chest tube duration（SMD-0.32 days,95%CI-0.47 to-0.17）,and shorter postoperative fasting time（SMD,-2.76 days;95%CI-2.98 to-2.54）.NIA patients showed higher levels of total lymphocytes and natural killer cells and higher T helper/T suppressor cell ratio,but lower levels of interleukin（IL）-6,IL-8 and C-reactive protein（CRP）.Moreover,NIA patients showed lower levels of fibrinogen,cortisol,procalcitonin and epinephrine.Conclusion:NIA enhances the recovery from VATS through attenuation of stress and inflammatory responses and stimulation of cellular immune function.Part 2:the application of non-tracheal intubation and intravenous anesthesia combined with intercostal nerve block guided by ultrasound in video-assisted thoracoscopic resection of pulmonary bullae or nodulesObjective:To investigate the safety and effectiveness of non-intubation anesthesia（NIA）in video-assisted thoracoscopic resection of pulmonary bullae or nodules.Methods:According to the principle of randomization and proportion of 1:1,using statistical software to generate random numbers,included patients were divided into three groups:intravenous anesthesia combined with ultrasound-guided intercostal nerve block group（NIA I group）,intravenous anesthesia combined with ultrasound-guided thoracic epidural anesthesia group（NIA II group）and traditional endotracheal intubation general anesthesia group（one-lung ventilation group,OLV group）,80 cases in each group.The 8 time points were respectively defined as T0（before anesthesia）,T1（15 minutes after OLV or NIA）,T2（30 minutes after OLV or NIA）,T3（30 minutes after intrathoracic operation）,T4（1 hour after intrathoracic operation）,T5（2 hours after operation）,T6（12 hours after operation）and T7（24 hours after operation）.Mean arterial pressure（MAP）and heart rate（HR）at T0-T5 time points were recorded,and the arterial blood gas analysis were performed at T0-T5 time points using Gem pemier 3000 automatic blood gas analyzer to observe the changes of Pa O₂/Fi O₂,Pa CO₂,intrapulmonary shunt,blood glucose and blood lactate.Then,the plasma level of interlekin（IL）-6,IL-8,C-reactive protein（CRP）and cortisol at T5-T7 time points were evaluated.Such variables of patient-controlled intravenous analgesia（PCIA）as drug,dosage,use time,background infusion,continuous infusion,bonus infusion and PCIA supplemental frequency were collected.Visual analogue scores（VAS）at T5-T7time points was evaluated.Satisfaction at T7 time points was quantified.Awakening time,time to discharge from the post-anesthesia care unit（PACU）,ambulation time,hospitalization days and expenses were compared between these three groups.The incidence of such adverse reactions as cough,reflux aspiration,hypoxemia,hypercapnia,vasoactive drug use,postoperative pulmonary infection,nausea and vomiting,throat discomfort and hoarseness were observed.Results:（1）Comparison of postoperative recovery between three groups:Compared with the OLV group,hospitalization days and expenses,awakening time,time to discharge from the PACU and ambulation time in the NIA I and NIA II group were both significantly decreased with significant statistical differences（P<0.05）,while the scores of discharge satisfaction was increased with significant statistical differences（P<0.05）.These indexes of postoperative recovery between the NIA I and NIA II group were lack of statistical differences（P>0.05）.（2）Comparison of postoperative analgesia between three groups:Compared with the OLV group,VAS score at T5-T7 time points in the NIA I and NIA II group were both significantly decreased with significant statistical differences（P<0.05）,and the PCIA supplemental frequency and dosage of fentanyl for rescue analgesia were simultaneously decreased with significant statistical differences（P<0.05）.There were no statistical differences observed on these indexes at each points between the NIA I and NIA II group（>0.05）.（3）Comparison of perioperative hemodynamics between three groups:Compared with the OLV group,MAP at T2 points in the NIA I and NIA II group were significantly decreased with significant statistical differences（P<0.05）,but it between the NIA I and NIA II group was similar（P=0.535）.MAP at other points between these three groups were both similar（P>0.05）.（4）Comparison of perioperative blood gas analysis between three groups:Compared with the OLV group,Pa O₂/Fi O₂at T1 points in the NIA I and NIA II group were significantly increased with significant statistical differences（P<0.05）.The level of lactate and Pa O₂at T1-T3 points in the NIA I group were both higher than that in the OLV group with significant statistical differences（P<0.05）.The intrapulmonary shunt at T1,T2 points in the the NIA I and NIA II group were both increased in comparison with the OLV group with significant statistical differences（P<0.05）.The Pa O₂/Fi O₂,Pa O_2,lactate level and intrapulmonary shunt at each points between the NIA I and NIA II group were lack of statistical differences（P>0.05）.（5）Comparison of perioperative stress and inflammatory response between three groups:Compared with the OLV group,the cortisol and IL-6 level at T5points in the NIA I and NIA II group were both increased while IL-6 level at T6and T7 points in the NIA I and NIA II group were decreased with significant statistical differences（P<0.05）.The IL-8 level at T5 points in the NIA I and NIA II group were higher than that in the OLV group,but the IL-8 level at T6points in the NIA II group were significantly increased compared with the OLV group with significant statistical differences（P<0.05）.The level of CRP at T5and T7 points in the NIA I and NIA II group were both higher than that in the OLV group.Between the NIA I and NIA II group,these indexes at each points were lack of statistical differences（P>0.05）.（6）Comparison of perioperative adverse reactions between three groups:Compared with the OLV group,the incidence of perioperative cough and use of vasoactive drugs in the NIA I and NIA II group were both significantly increased with significant statistical differences（P<0.05）.The incidence of perioperative hypoxemia and hypercapnia in the NIA II group were higher than that in the OLV group with significant statistical differences（P<0.05）.The incidence of postoperative nausea and vomiting,throat comforting and hoarseness in the NIA I and NIA II group were both significantly decreased in comparison with the OLV group with significant statistical differences（P<0.05）.The incidence of other adverse reactions at each points between NIA I and NIA II group were lack of statistical differences（P>0.05）.The incidence of intraoperative awareness,postoperative delirium,urinary retention and atelectasis between these three groups were lack of statistical differences（P>0.05）.Conclusion:Compared with OLV,NIA can significantly improve the postoperative recovery and perform effective analgesia for the patients undergoing video-assisted thoracoscopic resection of pulmonary bullae or nodules,which is associated with amelioration of oxygenation and attenuation of stress and inflammatory response.However,due to higher incidence of intrapulmonary shunt and hypercapnia,anesthesiologists should have high requirements for perioperative management and close observation of vital signs.Part 3:Application of spontaneous breathing versus mechanical ventilation in rats undergoing open thoracotomyObjective:We intend to explore the effect and mechanism of spontaneous breathing（NIV）,two lung ventilation（DLV）and one lung ventilation（OLV）on myocardial and lung injury in rats undergoing open thoracotomy.Methods:A total of 30 specific pathogen free Sprague-Dawley rats without limitation of sex,weighting 200～250 g,were included.These rats were randomly divided into five groups:blank control group（CON group）,NIV group,INB group,DLV group and OLV group（n=6）.The rats in the CON group were underwent intubation with spontaneous breathing;rats in the NIV group were given intubation with spontaneous breathing;rats in the INB group were given intubation with spontaneous breathing and intercostal nerve block;rats in the DLV and OLV group were respectively received endotracheal intubation with double or one lung ventilation.The rats in the NIV,INB,DLV and OLV group were both given open thoracotomy.After 2.0 h of ventilation,the serum,lung and cardiac tissues were harvested.The wet/dry weight（W/D）ratio,histopathology and ultrastructure changes were used to evaluate the degree of lung edema and injury.The levels of interleukin（IL）-1βand IL-6 in serum,left and right lung tissues were determined by enzyme linked immunosorbent assay（ELISA）.The m RNA and protein expression of nuclear factor-κB p65（NF-κB/p65）,NLRP3 inflammasome and triggering receptor expressed by myeloid cells-1（TREM-1）in the right and left lung were determined by RT-q PCR and Western Blot.To estimate the effect of pneumothorax,the ratio and count of neutrophils,ratio and count of eosinophils,IL-5,TNF-αand AQP-1level in serum and left and right lung tissues（ELISA）,m RNA and protein expressions of SNN1A and Caspase-3 in lung tissues（RT-q PCR and WB）were detected.The levels of epinephrine（E）,norepinephrine（NE）,5-hydroxytry-ptamine（5-HT）and glucose in serum,left and right lung tissues were measured by ELISA to compare the stress response levels of each group.Ultrastructure changes of heart,B-type natriuretic peptide（BNP）,troponin I（c Tn I）level（ELISA）,and malondialdehyde（MDA）,superoxide dismutase（SOD）,nitric oxide（no）and its synthetase（NOS）level（Test Kits）,and m RNA and protein expression of NF-κB/p65,NLRP3 and TREM-1（RT-q PCR and WB）in the cardiac tissues were determined to evaluate the injury of heart.Results:（1）Survival analysis:There were no rats died in the CON group.There was 1 rat died in the DLV group at 105 min after intubation,1 rat died in the OLV group at 110 min after intubation.There 2 rats died at the time interval of30-60 min,60-90 min and 90-120 min in the NIV group after intubation.Unfortunately,there were 2 rats died at the time interval of 0-30 min and 4 rats died at the time interval of 30-60 min in the INB group,and the survival time of each rat in the INB group were both less than 45 min.Survival rate in the NIV and INB group were 0.0%and significantly lower than that in the CON,DLV and OLV groups with statistical differences（P<0.05）;but the survival rates between the CON,DLV and OLV groups were lack of statistical differences（P>0.05）.The median survival time in the NIV and INB group were 37.5 min and 67.5 min with statistical differences（P<0.001）.（2）Lung injury:The structure of alveoli was disordered,pulmonary septum widened,edema,and infiltration of red blood cells and inflammatory cells in varying degrees in the lung tissues of INB＿L,INB＿R,DLV＿L and OLV＿R group.The lung injury in the tissues of INB＿R group was most severe with up-regulation of TREM-1,NLRP3 and NF-κB/p65.The right lung injury of OLV group were more severe than the left lung injury of DLV group.The level of IL-1βlevel in the INB group was higher than that in the CON group,and the IL-1βlevel in the right lung of INB group was higher than other subgroups with statistical differences（P<0.05）.（3）Effect of pneumothorax:The counts of neutrophils and eosinophils in the INB group were significantly increased in comparison with other groups with high level of IL-5 and TNF-αin serum and right lung tissues with statistical differences（P<0.05）.The SCNN1A and AQP-1 expression in the left lung of INB group were higher than other subgroups with statistical differences（P<0.05）.（4）Stress response:Stress response:The order of E level in the lung tissues from high to low was INB＿R group>DLV＿L group>OLV＿R group>INB＿L、OLV＿L group>DLV＿R、NIV＿R group>NIV＿L、CON group.The serum level of NE in the INB group was both higher than that in the NIV,DLV and OLV groups with statistical differences（P<0.05）.The serum levels of 5-HT in experimental groups were both increased compared with the CON group with statistical differences（P<0.05）.Furthermore,the levels of glucose in serum and lung tissues from INB＿R group were significantly higher than that in the other subgroups with statistical differences（P<0.05）.（5）Heart injury:In INB group,the arrangement of cardiomyocytes was disordered,and the number of mitochondria was increased,with the increase of BNP and c Tn I.Conclusion:（1）Long-time exposure（more than 30 min）to spontaneous breathing and INB rats favor severe stress and pneumothorax response,hypoxia,mediastinal swing and hemodynamic disorder resulting in respiratory and cardiac arrest.（2）INB and NIV in thoracotomy induces definite lung and heart injury,but the attenuation of inflammation were both similar with OLV.（3）NIV,INB,DLV and OLV both caused pneumothorax and stress reaction,and INB caused most severe systemic stress reaction.