肺保护性通气对单肺通气患者呼吸动力学、炎性因子及认知功能的影响

目的:探讨肺保护性通气对单肺通气(OLV)患者呼吸动力学、炎性因子及认知功能的影响。方法:选取2017年7月～2018年5月期间我院收治的择期行肺部手术的患者215例为研究对象。根据OLV方式的不同将患者分为传统OLV组(n=107)和保护性OLV组(n=108),比较两组OLV0.5 h(T1)、OLV1h(T2)等时间点的胸肺顺应性(CT)、气道阻力(Raw)、气道峰压(Ppeak)等指标情况,比较两组T1、T2、拔管后2 h(T3)白介素-6(IL-6)、白介素-8(IL-8)水平,比较两组术前、术后10 d第一秒用力呼气容积(FEV1)、一氧化碳弥散量(DLCO)、25%用力呼气流量(FEF25),比较两组术前、术后10 d、术后1个月简易精神状态量表(MMSE)评分,记录两组患者术后认知功能障碍发生率。结果:两组患者T2时间点CT均较T1时间点下降,但保护性OLV组高于传统OLV组(P0.05);两组患者T2时间点Raw、Ppeak较T1时间点升高,但保护性OLV组低于传统OLV组(P0.05)。两组患者T2、T3时间点IL-6、IL-8均较T1时间点升高,且T3时间点高于T2时间点(P0.05);保护性OLV组T2、T3时间点均低于传统OLV组(P0.05)。两组患者术前、术后1个月MMSE评分比较差异无统计学意义(P0.05);术后10 d,传统OLV组MMSE评分较术前、术后1个月降低,且术后10 d,保护性OLV组MMSE评分高于传统OLV组(P0.05);保护性OLV组术后认知功能障碍发生率显著低于传统OLV组(P0.05)。结论:OLV患者采用肺保护性通气的方式有助于改善患者呼吸动力学、肺功能以及认知功能,同时可以减轻机体炎性反应。     

肺保护性通气策略对老年患者腹腔镜结直肠癌手术的氧合功能及血浆炎症介质水平的影响

目的:探讨肺保护通气策略对老年患者行腹腔镜结直肠癌根治术肺部氧合功能及血清炎症介质水平的影响。方法:选择50例行择期腹腔镜结直肠癌根治术老年患者,ASA分级(美国麻醉医师协会体格情况评估分级)Ⅰ~Ⅱ级、年龄≥60岁,采用随机数字表法将其分为两组:VCV组和PCV组。在围术期行全麻机械通气中,VCV组采用容量通气模式,潮气量为8 m L/kg,PCV组采用肺保护通气,潮气量为6 m L/kg及5 cm H2O呼气末正压通气(positive end expiration pressure,PEEP),同时气腹后每30 min给予一次手法肺复张。记录患者气腹前5 min(T0)、气腹后5 min(T1)、气腹后30 min(T2)、气腹后60 min(T3)、气腹后120 min(T4)、气腹停止10 min后(T5)的呼吸力学指标、血流动力学指标于T0、T4、离开苏醒室时抽取血气,计算氧合指数(OI)值,于术前一天、T4、术后一天抽取静脉血,检测血浆CRP、IL-6的值。结果:与VCV组比较,PCV组在T4、T5时刻气道压降低,T4、T5肺顺应性增高(P<0.05)。两组患者血流动力学指标无明显差异。PCV组在离开苏醒室时氧合指数较高(P<0.05);PCV组在术后一天时刻IL-6和CRP值较低(P<0.05)。结论:肺保护性通气策略可以提高老年患者肺部氧合功能,减少炎症介质释放,减轻肺损伤。     

右美托咪定联合肺保护性通气策略对肺癌根治术患者氧化应激、炎症反应和免疫功能的影响

摘要 目的：探讨右美托咪定联合肺保护性通气策略对肺癌根治术患者氧化应激、炎症反应和免疫功能的影响。方法：选择我院行肺癌根治术患者110例,入选患者根据信封抽签法分为A组和B组,各为55例。A组接受右美托咪定联合传统通气策略,B组接受右美托咪定联合肺保护性通气策略,观察两组患者的氧合指数（OI）、氧化应激指标[超氧化物歧化酶（SOD）、丙二醛（MDA）]、炎症反应指标[白介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）]、免疫功能变化以及术后肺部并发症发生率。结果：B组单肺通气前即刻（T2）~恢复双肺通气15 min（T6）时间点OI高于A组（P<0.05）。B组术后72 h（T7）时间点CD3⁺、CD4⁺、CD4⁺/CD8⁺高于A组,CD8⁺低于A组（P<0.05）。B组T7时间点SOD水平高于A组,MDA水平低于A组（P<0.05）。B组T7时间点IL-6、TNF-α水平低于A组（P<0.05）。两组术后肺部并发症发生率组间对比无统计学差异（P>0.05）。结论：右美托咪定联合肺保护性通气策略可改善肺癌根治术患者氧合和炎症反应,有效减轻免疫抑制及氧化应激反应。     

不同俯卧位通气时间对中重度肺内/外源性ARDS患者的治疗效果

目的:探讨中重度肺内/外源性ARDS患者行不同时间俯卧位通气的治疗效果。方法:将中重度30例肺内/30例外源性ARDS患者分别行2h、4h俯卧位通气,观察患者APCHEII评分,氧合指数、胸片吸收情况、心率、平均动脉压、脱机拔管时间,出ICU时间。结果:四组患者APCHEII评分、心率、平均动脉压比较差异均无统计学意义(P0.05)。肺内源性ARDS患者行2 h、4 h俯卧位通气均能有效改善患者氧合指数,4 h组较2 h组氧合指数改善、胸片吸收情况更明显,4 h组在脱机时间、转出ICU时间均优于2 h组(P0.05);肺外源性ARDS患者行2 h、4 h俯卧位通气均能有效改善患者各项指标,但两组间无统计学差异(P0.05),且均优于肺内源性ARDS患者(P0.05)。结论:俯卧位通气可改善中重度肺内/外源性ARDS患者的病情,其对肺外源性ARDS患者效果更好,2 h俯卧位通气即能取得较好效果,而肺内源性ARDS患者需更长时间的俯卧位通气改善病情且预后较差。     

干预气道杯状细胞CLCA对ARDS小鼠损伤程度及炎症机制的影响

目的:探讨干预气道杯状细胞CLCA的表达与功能,对ARDS小鼠肺脏损伤程度的影响,并通过体外细胞研究探讨其机制。方法:制备LPS诱导的ARDS小鼠模型(ARDS组),并在此模型上分别进行干预,包括气道雾化吸入CLCA非特异性阻断剂尼氟灭酸(NFA)(NFA+ARDS组)、气道滴注CLCA特异性抗体(ab-CLCA3)(ab-CLCA3+ARDS组)。HE染色观察各组小鼠肺部病理及炎症特征,计算肺损伤评分。运用hCLCA1-siRNA抑制人正常支气管上皮细胞系16HBE中h CLCA1的表达,采用real-time RT-PCR法验证抑制效果后,检测各组细胞合成多种炎症因子m RNA水平的差异。结果:HE染色显示,ARDS组与NFA+ARDS组相比,肺部病理改变及炎症细胞浸润程度无明显差异,肺损伤评分也没有统计学差异(正常组:2.0±0.71;ARDS组:6.8±0.45,NFA+ARDS组7.4±0.89,P0.05)。与ARDS组相比,ab-CLCA3+ARDS组肺部病理损伤及炎症细胞浸润程度明显加重,肺损伤评分也升高(正常组:1.8±0.83;ARDS组:7.6±0.55,ab-mCLCA3+ARDS组9.8±0.83,P0.05)。real-time RT-PCR检测证实成功构建hCLCA1低表达的16HBE细胞系,同时real-time RT-PCR结果显示TNF-α和IL-1β的m RNA表达水平升高(P0.05)。结论:阻断气道CLCA功能区域,可以加重ARDS小鼠肺部病理损伤程度及炎症细胞浸润水平,提示气道杯状细胞CLCA在ARDS小鼠肺部炎症形成过程中发挥抑制性调节作用。     

保护性机械通气对开腹手术后肺功能的影响

目的：探讨开腹手术期间使用保护性通气策略对于术后肺功能的恢复和肺感染的影响。方法：选择ASAⅠ~Ⅱ级择期行腹部手术的患者50 例,预计手术时间大于2 h,体重指数<25%。将患者随机分为2 组：A组接受标准通气,潮气量8 mL/kg;B组接受保护性通气,潮气量为6 mL/kg,10 cmH2O PEEP 以及肺复张。术后第1、3 天进行肺功能实验,检测PaO2和SPO2。术前和术后第3 天进行胸部X 线和肺部感染评分。结果：与A 组患者比较,B 组患者术后第1、3 天的动脉氧合升高,且肺功能提高(P<0.05);术后第3 天肺不张的发生率降低(P<0.05);术后第1、3 天肺感染评分显著降低(P<0.05)。结论：大于2 h的腹部手术中,使用保护性通气可促进术后肺功能的恢复和减少肺感染的发生。     

HFOV联合PS对治疗新生儿ALI/ARDS的疗效及对肺动态顺应性的影响

摘要 目的：探讨高频振荡通气（HFOV）联合肺表面活性物质（PS）对治疗新生儿急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS）的疗效及对肺动态顺应性的影响。方法：选择2018年1月至2020年12月我院新生儿科收治的160例ALI/ARDS患儿进行研究,按照随机数表法分为观察组和对照组,每组80例。对照组患儿给予常频通气（CMV）模式联合PS治疗,观察组患儿给予HFOV模式联合PS治疗。比较两组患儿一般治疗情况、治疗前后肺动态顺应性、动脉血氧分压（PaO₂）、动脉二氧化氮分压（PaCO₂）、氧合指数（OI）、血清肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-6、IL-10的变化,以及治疗期间并发症发生情况。结果：观察组胸片恢复正常时间、机械通气时间、氧暴露时间、ICU停留时间、住院时间结果均明显短于对照组（P＜0.05）,两组患儿病死率相比较,无统计学意义（P＞0.05）;治疗后12 h、24 h、48 h时,观察组肺动态顺应性及PaO₂、OI结果明显高于对照组,PaCO₂明显比对照组低,差异有统计学意义（P＜0.05）;治疗后48 h时,观察组血清TNF-α、IL-6水平均明显低于对照组,IL-10明显比对照组高,差异有统计学意义（P＜0.05）;两组治疗期间,呼吸机相关性肺损伤、颅内出血、气漏、呼吸道感染的总发生率比较,无统计学意义（P＞0.05）。结论：HFOV联合PS治疗新生儿ALI/ARDS疗效明显,可有效改善患儿肺动态顺应性,促进血气分析指标恢复,且可降低炎症因子的表达,值得推广应用。     

大承气汤辅助治疗ARDS患者对其pH、PaO2/FiO2和氧化应激状态的影响

目的:观察大承气汤辅助治疗ARDS患者对其pH、氧合指数(PaO_2/FiO_2)及氧化应激状态的影响。方法:选择2014年8月~2016年8月于成都中医药大学临床医学院就诊的82例ARDS患者,按治疗方式的不同随机分为对照组与实验组,对照组接受常规治疗,实验组在对照组的基础上联合大承气汤治疗,两组均持续用药7天。观察两组ICU住院时间、机械通气时间、不良反应的发生情况、治疗前后pH、PaO_2/FiO_2、血气超氧化物歧化醇(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醇(MDA)水平的变化。结果:实验组ICU住院时间、机械通气时间及不良反应的发生率均显著短于或低于对照组(P0.05)。治疗前,两组pH、PaO_2/FiO_2、血清SOD、GSH-Px、MDA水平比较差异无统计学意义(P0.05);治疗后,两组pH、PaO_2/FiO_2、血清SOD、GSH-Px水平均较治疗前显著上升,且实验组PaO_2/FiO_2、血清SOD、GSH-Px水平明显高于对照组,两组血清MDA水平均较治疗前明显降低,且实验组血清MDA水平显著低于对照组(P0.05)。结论:大承气汤辅助治疗ARDS能够有效改善患者pH、PaO_2/FiO_2,缓解氧化应激状态,利于患者恢复。     

使用机械通气联合限制性液体复苏对重度颅脑损伤患者的急救效果及对远期认知功能影响

摘要 目的：探讨使用机械通气联合限制性液体复苏对重度颅脑损伤患者的急救效果及对远期认知功能影响。方法：选取我院2020年1月到2022年12月急诊收治的90例重度颅脑损伤患者作为研究对象,应用随机数字表法将所有患者分为观察组与对照组,每组45例。所有患者均采取常规重型颅脑损伤治疗,对照组患者在损伤后立即给予机械通气,并采取常规液体复苏措施进行治疗。观察组在损伤后立即给予机械通气,并采取限制性液体复苏治疗,对比两组患者急救效果,急救治疗前与急救治疗后1 h的血气指标变化情况,急救治疗前与急救治疗后1 d的血尿素氮（BUN）、血清肌酐（Scr）、乳酸、肌酸激酶（CK）相关生化指标表达水平,最后分别在患者苏醒时、术后3 d、6 d、10 d检测两组患者S100B蛋白与褪黑素表达水平。结果：观察组患者苏醒时间、说话时间、总输液量以及死亡率明显低于对照组,观察组GOS评分明显高于对照组（P＜0.05）;治疗前两组患者血氧饱和度（SpO₂）、动脉血二氧化碳分压（PaCO₂）水平对比无明显差异（P＞0.05）,治疗后,对照组SpO₂水平降低,观察组无明显变化,两组患者PaCO₂水平均降低,且观察组低于对照组（P＜0.05）;治疗前两组患者BUN、Scr、乳酸、CK相关指标表达水平对比无明显差异（P＞0.05）,治疗后对照组患者CK水平升高,观察组无明显变化,且观察组明显低于对照组,BUN、Scr、乳酸水平均降低,且观察组明显低于对照组（P＜0.05）;两组患者苏醒时S100B 蛋白、褪黑素对比无明显差异（P＞0.05）,术后3 d、6 d、10 d S100B 蛋白明显降低,且观察组低于对照组,术后3 d、6 d、10 d褪黑素明显升高,观察组高于对照组（P＜0.05）。结论：使用机械通气联合限制性液体复苏能够提升重度颅脑损伤患者的急救效果,降低患者死亡率,且能够及时改善患者血氧饱和度、动脉血二氧化碳分压相关血气指标水平,减轻对患者心功能、肾功能带来的损伤,同时能够降低对患者神经功能产生的损伤情况。     

双水平气道正压通气(BIPAP)呼吸机治疗COPD并Ⅱ型呼吸衰竭患者的疗效评估

目的:探讨双水平气道正压通气治疗慢性阻塞性肺疾病(COPD)合并Ⅱ型呼吸衰竭的临床疗效。方法:选取我院收治的COPD合并Ⅱ型呼吸衰竭患者84例,随机分为对照组和研究组,每组42例。对照组患者给予常规治疗,研究组患者在常规治疗基础上给予双水平气道正压通气治疗。观察并记录两组患者治疗前后动脉血气分析、肺功能变化以及临床疗效。结果:研究组治疗有效率高于对照组,差异具有统计学意义(P0.05);与治疗前比较,两组患者治疗后PaO_2、SaO_2、pH均升高,而PaCO_2均降低,差异具有统计学意义(P0.05);与对照组比较,研究组治疗后PaO_2、SaO_2、pH水平较高,PaCO_2水平较低,差异具有统计学意义(P0.05);与治疗前比较,两组患者治疗后FEV1、FVC、FEV1%pre和FEV1/FVC均升高,差异具有统计学意义(P0.05);与对照组比较,研究组治疗后FEV1、FVC、FEV1%pre和FEV1/FVC较高,差异具有统计学意义(P0.05);研究组住院时间、气管插管率均低于对照组,差异具有统计学意义(P0.05)。结论:双水平气道正压通气(BIPAP)呼吸机治疗COPD并Ⅱ型呼吸衰竭患者疗效确切,能显著改善肺功能及动脉血气指标,值得推广。     

生地黄对内毒素诱导的急性肺损伤的保护作用

目的:以中医辨证论治为基础,研究生地黄对急性肺损伤/急性呼吸窘迫综合征(acute lung injury/acute respiratory distress syndrome,ALI/ARDS)的干预作用。方法:将大鼠分为对照组、模型组、生地黄预防组、生地黄治疗组,通过气管注射脂多糖(LPS)制备大鼠ALI/ARDS模型,酶联免疫法(ELISA)测定支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素-6(interleukin-6,IL-6)含量的变化,考马斯亮蓝法测定BALF中总蛋白含量,BALF细胞悬浮液离心涂片Giemsa染色后光镜下细胞分类计数,H.E.染色肺部组织并通过光镜观察其形态学变化,分析生地黄水提物对ALI的保护作用。结果:生地黄干预组BALF中TNF-α、IL-6含量明显降低(P0.0),蛋白含量明显降低(P0.0),中性粒细胞数(Polymorphonuclear cells,PMN)和炎症细胞总数明显降低(P0.0),肺部病理损伤减轻。结论:生地黄对ALI可能具有保护作用,对ALI/ARDS可能具有潜在的治疗价值。     

Surfactant Therapy for Patients with ARDS After Cardiac Surgery

This multicenter study investigated the possibility of reducing mortality rate by administering natural lung surfactant additional to standard therapy to treat patients after cardiac surgery who developed an acute respiratory failure (ARDS/ALI).

A total of 78 patients (1998–2002) diagnosed with ALI or ARDS were enrolled in the study; patients were considered for study entry only if they developed ALI/ARDS within 72h after cardiac surgery. A total of 36 patients (2000–2002) received Surfactant-BL via bronchoscope at a dose of 3 mg/kg twice a day, and 42 patients (1998–2000) served as the historical control.

Within 24h after the first Surfactant-BL administration the PaO₂/FiO₂ ratio increased from (mean ± SEM) 129.7 ± 9.9 mm Hg to 187.6 ± 17.6 mm Hg (p < 0.01), FiO₂ decreased from (mean ± SEM) 0.71 ± 0.03 to 0.56 ± 0.03 (p < 0.01), and 69.4% of the patients treated with surfactant were weaned from the ventilator compared with 50% of the control group during a 28-day period. The mortality rate among patients treated with Surfactant-BL was 30.6% compared with 50% in the control group.

In conclusion, early administration of Surfactant-BL leads to the reduction of mortality in cardiac patients who develop postoperatively an ALI or ARDS.     

急性肺损伤的生物标记物

急性呼吸窘迫综合征(ARDS)和急性肺损伤(ALI)多由低氧性呼吸衰竭引起,导致高通透性肺水肿,临床上有较高的发病率与死亡率。近十年来,针对血浆和支气管肺泡灌洗液中相关生物标记物的研究为探索急性肺损伤的病理生理机制指明了新的方向。个别生物标记物已在一些大型、多中心ARDS试验中得到证实。但迄今仍没有一个或一组生物标记物常规应用于临床。随着人类对ALI发病机制理解的进一步深入,或许不久的将来,生物标记物会真正应用于评估疾病的严重程度和预后。本文将概述近年来ALI相关生物标记物的研究进展。     

细胞因子在ARDS发病机制中的作用

细胞因子是由多种细胞产生的多肽或低分子糖蛋白,在人体内含量极微,在pg水平就发挥作用。作为特异性免疫反应和非特异性免疫反应的蛋白质,细胞因子以自分泌、旁分泌、或内分泌方式产生,与相应的细胞表面受体结合,在局部或全身发挥复杂的生物学效应,它们的代谢异常和疾病的发生、发展有着密切的关系。有些细胞因子已应用于临床的生物学治疗,具有深远的临床应用价值,故对细胞因子的研究将是一个越来越重要的课题。急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)发病机制错综复杂,大量临床和实验室研究证明多种效应细胞释放的炎症介质是造成ARDS的"中心环节",其中TNF-α、IL-1、IL-8、IL-10、CXC趋化因子等细胞因子在ARDS发病中的作用尤为重要。本文就细胞因子在ARDS发病机制中的作用做一综述。     

Liver carboxylesterase cleaves surfactant protein (SP-) B and promotes surfactant subtype conversion

Conversion of the biophysically active large surfactant aggregate subtype of alveolar surfactant into the less surface active small surfactant aggregates occurs in vitro and in vivo, possibly in dependency of a carboxylesterase, entitled surfactant convertase. The substrate has yet not been safely identified. Utilizing the in vitro cycling assay we investigated conversion of an organic rabbit lavage extract reconstituted with SP-A. Porcine liver carboxylesterase, which is closely related to surfactant convertase, induced subtype conversion to a similar degree as compared with native lavage fluid containing endogenous convertase. In addition, we asked for cleavage products of SP-B and identified a approximately 12 kDa band upon cycling with liver carboxylesterase, having the same N-terminus as mature SP-B. A band of same molecular weight was found in native lavage fluid after in vitro conversion mediated by the endogenous convertase. We conclude that SP-B plays a pivotal role during subtype conversion and represents the substrate for surfactant convertase.     

Lung clearance index in adults with non-cystic fibrosis bronchiectasis

Background

Lung clearance index (LCI) is a measure of abnormal ventilation distribution derived from the multiple breath inert gas washout (MBW) technique. We aimed to determine the clinical utility of LCI in non-CF bronchiectasis, and to assess two novel MBW parameters that distinguish between increases in LCI due to specific ventilation inequality (LCI_vent) and increased respiratory dead space (LCI_ds).

Methods

Forty-three patients with non-CF bronchiectasis and 18 healthy control subjects underwent MBW using the sulphur hexafluoride wash-in technique, and data from 40 adults with CF were re-analysed. LCI_vent and LCI_ds were calculated using a theoretical two-compartment lung model, and represent the proportional increase in LCI above its ideal value due to specific ventilation inequality and increased respiratory dead space, respectively.

Results

LCI was significantly raised in patients with non-CF bronchiectasis compared to healthy controls (9.99 versus 7.28, p < 0.01), and discriminated well between these two groups (area under receiver operating curve = 0.90, versus 0.83 for forced expiratory volume in one second [% predicted]). LCI, LCI_vent and LCI_ds were repeatable (intraclass correlation coefficient > 0.75), and correlated significantly with measures of spirometric airflow obstruction.

Conclusion

LCI is repeatable, discriminatory, and is associated with spirometric airflow obstruction in patients with non-CF bronchiectasis. LCI_vent and LCI_ds are a practical and repeatable alternative to phase III slope analysis and may allow a further level of mechanistic information to be extracted from the MBW test in patients with severe ventilation heterogeneity.     

Mechanical Stretch Inhibits Lipopolysaccharide-induced Keratinocyte-derived Chemokine and Tissue Factor Expression While Increasing Procoagulant Activity in Murine Lung Epithelial Cells

Previous studies have shown that the innate immune stimulant LPS augments mechanical ventilation-induced pulmonary coagulation and inflammation. Whether these effects are mediated by alveolar epithelial cells is unclear. The alveolar epithelium is a key regulator of the innate immune reaction to pathogens and can modulate both intra-alveolar inflammation and coagulation through up-regulation of proinflammatory cytokines and tissue factor (TF), the principal initiator of the extrinsic coagulation pathway. We hypothesized that cyclic mechanical stretch (MS) potentiates LPS-mediated alveolar epithelial cell (MLE-12) expression of the chemokine keratinocyte-derived cytokine (KC) and TF. Contrary to our hypothesis, MS significantly decreased LPS-induced KC and TF mRNA and protein expression. Investigation into potential mechanisms showed that stretch significantly reduced LPS-induced surface expression of TLR4 that was not a result of increased degradation. Decreased cell surface TLR4 expression was concomitant with reduced LPS-mediated NF-κB activation. Immunofluorescence staining showed that cyclic MS markedly altered LPS-induced organization of actin filaments. In contrast to expression, MS significantly increased LPS-induced cell surface TF activity independent of calcium signaling. These findings suggest that cyclic MS of lung epithelial cells down-regulates LPS-mediated inflammatory and procoagulant expression by modulating actin organization and reducing cell surface TLR4 expression and signaling. However, because LPS-induced surface TF activity was enhanced by stretch, these data demonstrate differential pathways regulating TF expression and activity. Ultimately, loss of LPS responsiveness in the epithelium induced by MS could result in increased susceptibility of the lung to bacterial infections in the setting of mechanical ventilation.