Beta-2-adrenoceptor agonists as inhibitors of lung vascular permeability to radiolabelled transferrin in the adult respiratory distress syndrome in man

Increased lung vascular permeability leading to increased plasma protein extravasation and accumulation (PPA) is a characteristic feature of acute lung injury. Using a previously described technique, PPA was monitored in the lungs of patients with the adult respiratory distress syndrome (ARDS)--an extreme example of acute lung injury in man. An external radiation probe detector was used to monitor the pulmonary accumulation of the plasma protein transferrin radiolabelled in-vivo with 113mIn. Ten patients with ARDS exhibiting increased PPA indices (greater than 1.0 x 10(-3)/min) were given an intravenous infusion of terbutaline (7 micrograms/kg) over 30 min. Of the four patients in whom the post-drug PPA indices remained within the ARDS range, none survived, whilst five of the six patients in whom the post-drug PPA indices were reduced to below 1.0 x 10(-3)/min survived. PPA indices prior to the administration of terbutaline were not significantly different between the survivor (n = 5) and non-survivor (n = 5) groups. There was a significant decrease in the PPA indices following terbutaline in survivors (p less than 0.01) but not in non-survivors. Thus beta-2-agonists in therapeutic doses can inhibit increased lung vascular permeability in man. These findings may have prognostic and therapeutic implications for beta-2-agonists in ARDS.     

肺脏超声在新生儿呼吸窘迫综合征中的应用进展

新生儿呼吸窘迫综合征(respiratory distress syndrome,RDS)是新生儿的急危重症之一,如不及时治疗会危及患儿生命,因此,早期诊断尤为重要。国际及国内大量研究证明,超声在RDS诊断与鉴别诊断、并发症的诊断及指导治疗等方面有诸多优势,随着技术不断进步和人们观念的不断转变,超声检查技术有望成为诊断RDS的首要辅助检查方法。     

Acute respiratory distress syndrome: imaging of the injured lung.

In patients with the acute respiratory distress syndrome (ARDS), there is non-specific but widespread exudation of oedema and inflammatory fluid into the lungs. The clinical corollary (dyspnoea, refractory hypoxia, reduced pulmonary compliance and diffuse pulmonary infiltrates) is catastrophic and generally associated with a poor outcome. Imaging is integral to the care of these critically ill patients on the intensive care unit. In the present review, the radiological changes on plain radiography and computed tomography (CT) in patients with ARDS are discussed. Particular attention is directed at the appearances on CT: the relationships between CT features, histopathological changes and the inevitable alterations in pulmonary physiology are explored.     

超声诊断新生儿呼吸窘迫综合征的临床价值探讨

目的探讨超声检查对新生儿呼吸窘迫综合征患儿的诊断价值。方法回顾性分析2015年7月~2017年10月在我院治疗的96例新生儿呼吸窘迫综合征的临床资料,根据胸部X线检查结果,将患儿划分为轻症组(55例)与重症组(41例)。所有患儿均需在治疗前、治疗后12h、治疗后24h接受超声检查,比较两组超声检查结果、超声评分。结果轻症组超声评分低于重症组,差异有统计学意义(P<0.05);治疗前,各组PS治疗与非PS治疗患儿的超声评分对比,差异无统计学意义(P>0.05);治疗后各时间段,各组非PS治疗患儿的超声评分均高于PS治疗,差异有统计学意义(P<0.05)。结论超声检查可有效对新生儿呼吸窘迫综合征患儿病情程度做出有效评价,此外,超声检查评分可作为评价患儿病情以及量化病情的重要指标。     

国产肺表面活性物质珂立苏治疗足月新生儿呼吸窘迫综合征临床疗效评价

目的观察珂立苏治疗足月新生儿呼吸窘迫综合征（RDS）临床疗效。方法对符合足月新生儿RDS诊断标准、且家长同意 使用外源性肺表面活性物质（PS）的患儿,根据家长意愿分为两组,即珂立苏治疗组55例和固尔苏治疗组47例。在相同的综合治疗基础上比较两组患儿补充外源性PS制剂前后的血气变化、主要呼吸机参数、机械通气时间、氧疗天数、住院天数、住院费用以及并发症等情况。结果给予PS制剂后8h、24h、48h两组患儿的氧合及通气功能（PaO2﹑Pa-CO2）明显改善（P〈0.01）,主要呼吸机参数（PIP﹑PEEP、FiO2）等指标均明显降低（P〈0.01）,使用珂立苏或固尔苏患儿在各观察点上述指标比较均无差异（P〉0.05）。两组患儿的机械通气时间珂立苏组（163.61±76.81）h,固尔苏组（188.57±76.74）h（t=1.560,P=0.122）;氧疗天数珂立苏组（11.58±4.64）d,固尔苏组（11.93±4.39）d,t=0.372,P=0.710;住院天数珂立苏组（20.72±6.06）d,固尔苏组（20.14±4.77）d,t=0.212,P=0.832;住院费用珂立苏组（32758.41±10451.24）元,固尔苏组（35980.24±9855.57）元,前者节约9.0%（t=2.084,P=0.037）。两组患儿并发症（MOSF、PPHN、急性肾衰、肺出血、DIC等）发生率均无显著性差异（P〉0.05）。结论国产肺表面活性物质珂立苏治疗足月新生儿RDS与进口固尔苏具有相似的疗效,但珂立苏能在一定程度上减少住院费用。     

创伤患者急性呼吸窘迫综合征的诊治策略——掌握规律,实施时效与整体性救治

创伤现已成为我国人口死亡的常见原因,创伤患者并发创伤后急性呼吸窘迫综合征(ARDS)是创伤后数天至数周内发生死亡的重要因素之一.目前急诊外科在救治创伤后ARDS时仍存在一定不足,一方面与早期识别率不高有关,另一方面也与识别后救治措施不当相关.急诊外科医师只有熟练掌握创伤后ARDS的规律,才能早期识别创伤后ARDS,而实施时效性和整体性相结合的救治原则,可有效提高救治率.     

雷洛昔芬对大鼠急性肺损伤保护作用的研究

目的 探讨雷洛昔芬对大鼠急性肺损伤(acute lung injury,ALI)的保护作用.方法 30只SD雄性大鼠按随字数字表法分为三组:二次打击前用药组(10只)、二次打击中用药组(10只)和对照组(10只).所有大鼠腹腔注射5 mg/kg LPS,并分别于LPS腹腔注射前1 h和腹腔注射后14 h对二次打击前用药组和二次打击中用药组用雷洛昔芬30 mg/kg灌胃,LPS腹腔注射后16 h,所有大鼠均用戊巴比妥钠按40 mg/kg行腹腔注射麻醉,股动脉插管监测平均动脉压(MAP),气管内滴入pH为1.2,0.5 ml/kg盐酸.盐酸滴入前及滴入后30,90 min和4 h查动脉血气分析,4 h后每组中选取5只大鼠行[18F]FDG microPET胸部扫描,而后取肺组织进行组织病理学观察.结果 血气分析显示二次打击中用药组大鼠能显著改善肺的氧合功能,并能使MAP稳定,[18F]FDG吸收度及肺组织病理评分在对照组分别为9.01±1.58,12.6±0.97,显著高于二次打击中用药组的4.67±1.33(P<0.01)和8.20±1.23(P<0.01).结论 雷洛昔芬对大鼠ALI具有明显保护作用;[18F]FDG microPET能很好地评价ALI时肺内的炎症反应.     

Determinants of diagnostic accuracy in pulmonary scintigraphy for pulmonary capillary protein leak associated with adult respiratory distress syndrome (ARDS): A technical note

Radionuclide assessment of pulmonary capillary protein leak using [^99mTc] human serum albumin (^99mTc-HSA) was first reported from our laboratory. In this study we investigated the impact of 1) sampling time post tracer injection, and 2) lung region assignment, on diagnostic accuracy between 2 groups (controln=20 and ARDSn=20). Each patient received 370 MBq^99mTc-HSA i.v. and was imaged for 45 min. The slope index (SI) [change in lung: heart activity ratio/min] was calculated from 11 computer assigned lung regions for intervals of 5–15 (early [E]) and 15–45 (late [L]) min. The diagnostic accuracy of E vs L SI calculations for the 11 regions was evaluated by stepwise logistic regression. E SI data and L SI data from the lower 1/3 of the lung did not achieve significance for inclusion in the discriminant model (P<0.05). In the nine remaining regions L SI was significant. Optimal discrimination was achieved from L SI data obtained from a region confined to the lateral half of the mid 3rd of the lung field (sensitivity 81%, specificity 85%, accuracy 83%). The results confirm that: 1) a late (15–45 min) sampling period and 2) proper region assignment are necessary to maximize accuracy of this technique.Supported by NIH Grant # 1R23GM27245-01     

肺超声评分评估新生儿呼吸窘迫综合征及预后的价值

目的 分析新生儿呼吸窘迫综合征(NRDS)的肺超声图像特点,以及肺超声评分(LUS)对NRDS病情评估的可行性.方法 选取我院早产儿病房收治的80例NRDS患儿为观察组,根据病症严重程度分为非危重组(26例)、危重组(34例)和极危重组(20例);同时期收治的非肺部疾病的早产儿60例为对照组.分别对两组治疗前行肺部超声...     

肌球蛋白轻链激酶在急性肺损伤/急性呼吸窘迫综合征中的作用

肺气血屏障功能缺陷在急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)病理生理改变过程中居于中心地位,而肌球蛋白轻链激酶(MLCK)通过磷酸化肌球蛋白轻链(MLC)对其有调节作用.MLCK主要分为平滑肌型MLCK(smMLCK)、内皮型MLCK(eMLCK)和激酶相关蛋白(KRP).它们由同一基因编码.eMLCK在ALI/ARDS中尤为重要.eMLCK有4个亚型:eMLCK2,eMLCK3a,eMLCK3b和eMLCK4,其中eMLCK2是优势亚型.脂多糖(LPS)、血小板活化因子(PAF)、凝血酶、缺血再灌注(I/R)、非正常机械应激都可以诱发ALI/ARDS,MLCK在其中发挥了重要作用.机制是MLCK使MLC磷酸化,导致细胞连接破坏,细胞骨架重排,内皮细胞收缩,并最终增加肺上皮细胞和肺内皮细胞的通透性.鉴于MLCK在ALI/ARDS中的重要性,它必将成为一个潜在的治疗靶点,在ALI/ARDS新药的研发和防治中发挥重要作用.     

急性呼吸窘迫综合征犬模型的CT表现及临床病理对照

目的 应用MSCT观察急性呼吸窘迫综合征(ARDS)犬模型的CT表现,并与临床、病理进行对照研究.方法 健康比格犬15只,随机数字表法分为实验组(10只)及对照组(5只).通过犬右侧股深静脉注射油酸进行造模,注射油酸后每10 min为1个观察点,共观察5个时间点.最后以临床测量动脉血氧合指数(PaO2/FiO2)≤200 mmHg时,确诊为ARDS成模,此时为1个观察点,通过CT扫描观察6个不同时间点犬肺部CT表现,同时记录临床数据并观察实验犬肺湿干比及病理改变.采用2个独立样本t检验对实验前及建模成功时的PaO2/FiO2及肺动脉楔压(PCWP)进行分析.结果 实验组在油酸注射(92.9±8.5)min后形成ARDS模型,实验组实验前PaO2/FiO2及PCWP分别为(466.7±27.0)、(8.6±1.8)mmHg,建模成功时分别为(164.1±21.1)、(9.9±3.6)mmHg,前后差异有统计学意义(t值分别为26.04、-1.02,P值均＜0.05).实验组犬大体病理可见脏层胸膜张力大,呈紧绷状态,肺表面出现弥漫充血、水肿,两下肺呈朱红色类似肝组织,镜下主要表现为肺水肿、炎性细胞渗出及透明膜形成.肺湿干比重为10.4±0.7,对照组为5.3±0.8,两者差异有统计学意义(t=4.80,P＜0.05).在ARDS成模过程中CT表现具有一定规律性,最早出现的是磨玻璃密度影,以肺野外带及肺野背部明显,偶尔会有肺实变影和代偿性的肺透亮度增高影;当犬ARDS成模时,典型的CT表现为两肺弥漫分布磨玻璃密度影(10只)、大片肺实变影(10只)、小叶间隔增厚(9只)、肺透亮度增高(7只)、胸腔积液(2只)及胸膜增厚(1只),呈不规则分布,病灶以肺的重力区明显.结论 MSCT可观察ARDS的前期影像表现,可为临床诊断提供可靠的影像资料.     

分次灌注海水致兔呼吸窘迫综合征模型的建立

目的通过向兔气管插管内灌入海水，建立海水淹溺致急性呼吸窘迫综合征模型。方法14只新西兰大白兔被随机平分为C组（对照组，无任何处理）和S组（海水组，用海水灌注）。观察分次适量海水灌入气管插管后症状学、血气分析、血液动力学、血清中肿瘤坏死因子（TNF—α）和白细胞介素-6（IL-6）的变化。2h后给每组试验兔拍摄肺CT片，并观察其组织病理学变化。结果与C组相比，S组的O2和CO2指数显著降低（P〈0．01），呼吸动力学和血液动力学的情况明显恶化。TNF—α和IL-6增高，这一结果提示肺损伤发生于兔被海水灌注之后。另外，还发现模型兔有明显的肺水肿、肺泡隔断裂和炎性渗出。结论成功复制了既符合海水淹溺的实际情况，又符合国内外急性呼吸窘迫综合征诊断标准的海水淹溺致急性肺损伤动物模型。     

MMP-2 mRNA在内毒素致兔急性肺损伤中的作用及美洛昔康的影响

目的观察内毒素（ET）致兔急性肺损伤（ALI）时肺组织中基质金属蛋白酶-2（MMP-2）mRNA的表达变化及美洛昔康对兔急性肺损伤干预的机制。方法将24只大耳白兔随机分为生理盐水对照组（A组）、内毒素致伤组（B组）、内毒素致伤及美洛昔康干预组（C组），每组8只。B组用ET（700μg／kg）一次性静脉注射方法复制兔ALI模型，C组在B组的基础上用美洛昔康（2．5mg／kg）进行干预，观测兔动脉血气、肺组织湿重／干重比（W／D）、肺水含量、肺组织病理学改变、肺组织中MMP-2 mRNA的表达变化。结果与A组比较，B组氧合指数明显降低，肺组织出现水肿、出血、炎性细胞浸润，W／D比值、肺水含量及肺组织MMP-2 mRNA表达明显增加；C组氧合指数未见明显下降，W／D比值、肺水含量、肺组织中MMP-2 mRNA表达较B组减少，病理改变亦较B组轻。结论在ALI时，MMP-2 mRNA表达上调，美洛昔康可抑制MMP-2 mRNA的表达，在一定程度上对内毒素性ALI产生保护作用。     

盐酸戊乙奎醚联合地塞米松对兔爆震伤急性呼吸窘迫综合征的治疗作用

目的 探讨盐酸戊乙奎醚(PHC)联合地塞米松(DXM)对兔胸部爆震伤ARDS的治疗作用.方法 采用健康新西兰大白兔制作兔胸部爆震伤ARDS模型,将符合ARDS诊断标准的兔随机分为5组:B组,爆炸致ARDS组(n=10)；C组,低剂量(0.8mg/kg)PHC组(n=9)；D组,高剂量(1.5mg/kg) PHC组(n=...     

内毒素致兔急性肺损伤时磷脂酶A2激活及1,6-二磷酸果糖拮抗作用的研究

目的研究内毒素(ET)致大耳白兔急性肺损伤(ALI)过程中磷脂酶A2的变化和1,6-二磷酸果糖(FDP)的拮抗作用,探讨FDP对ET所致ALI的治疗作用。方法大耳白兔随机分为对照组(A组)、ET致伤组(B组)、ET致伤 FDP干预组(C组)。A组:静脉注射生理盐水2ml/kg。B组:将内毒素按500μg/kg溶于2ml生理盐水后经颈静脉插管一次注射完毕,随后注射生理盐水1次,液体总量为2ml/kg。C组:内毒素使用剂量和方法同致伤组,随后缓慢经静脉注射FDP(300mg/kg)的生理盐水溶液,液体总量同为2ml/kg。各组分别于0h、0·5h、2h、4h及6h等不同时点测定呼吸频率、心率、血压、血气分析及血清中PLA2活性;于6h点处死动物,测定肺组织PLA2活性,并行肺组织光镜和电镜下病理学观察。结果静注ET后,B组动物与A组相比较,出现典型的ALI表现,血清和肺组织PLA2活性显著增高(P<0·01),而C组动物各项指标则介于A组和B组之间。同时,肺组织病理学观察显示,B组动物肺组织出现了明显的病理损害,而C动物肺组织的病理损害程度较轻。结论PLA2激活是ET所致ALI发病过程中重要的致伤因素。FDP可抑制PLA2激活,从而对ET所致的兔早期ALI有一定的保护作用。     

Comparison of radiographic infiltration versus pulmonary function in severely traumatized patients with and without adult respiratory distress syndrome: Correlation of lung structure and function

Lung structural changes were evaluated by radiographic infiltration and compared with functional changes by pulmonary venous admixture or shunt ( ) and blood gases (PaO₂/FiO₂ ratio, which is the ratio of arterial oxygen tension to oxygen concentration of inspired gas) in 70 consecutive severely traumatized patients. Of these, 36 (51%) developed adult respiratory distress syndrome (ARDS) by clinical and physiologic criteria, and 34 (49%) did not develop ARDS; 42 patients sustained direct pulmonary injury from penetrating stab or gunshot wounds; 24/36 (67%) of those with ARDS and 28 (40%) of the entire series died. The study showed a rough direct correlation of a semiquantitative infiltration score with pulmonary shunt and an indirect correlation with the PaO₂/FiO₂ ratio during the initial resuscitation and the subsequent posttrauma course in both ARDS and non-ARDS patients. The temporal pattern of the infiltration score closely paralleled that of the pulmonary shunt pattern and inversely paralleled the PaO₂/FiO₂ ratios throughout the period of observation, indicating that radiographic structural changes developed concomitantly with functional changes. To avoid confounding issues, we studied only young, previously healthy trauma victims without head injury. Data from patients with direct lung injury were stratified and evaluated separately. The earliest observed changes most often occurred in the upper and middle lung fields; by contrast, most mechanically ventilated trauma patients had varying degrees of infiltration in the bases with some dysfunction, but not enough to meet ARDS diagnostic criteria.     

兔内毒素性急性肺损伤中磷脂酶A2致伤机制及氯喹保护作用的研究

目的研究大肠杆菌内毒素(ET)致兔急性肺损伤(ALI)过程中磷脂酶A2(PLA2)激活和氧化应激的致伤机制以及氯喹的保护作用.方法 24只大耳白兔随机均分为对照组、ET致伤组、ET致伤+氯喹治疗组.静脉注射ET(500μg/kg)致兔ALI,观测动脉血气、血清和肺组织中PLA2的活性、肺组织脂质过氧化物(LPO)和超氧化物歧化酶(SOD)含量的变化,并观察氯喹对ALI病理生理过程的影响.结果静注ET后,兔出现动脉血氧分压下降、肺内白细胞扣押等ALI病理改变.ET组肺组织LPO增高(P<0.05),SOD明显降低(P<0.05),PLA2活性增高(P<0.01);病理检查见肺水肿,部分肺组织片状出血,伴局灶性肺不张和肺气肿;超微病理改变表现为Ⅰ型、Ⅱ型肺泡上皮细胞损伤.氯喹处理组动脉血氧分压未见下降,肺组织PLA2活性低于ET组,LPO降低,SOD增高;病理检查见轻度肺水肿,炎细胞浸润较ET组少;肺组织超微病理检查显示损伤轻于ET组.结论静脉注射ET可复制兔ALI动物模型,PLA2激活及氧化应激在此病理生理过程中起重要作用;氯喹对ET所致的兔ALI具有一定的保护作用.     

Stenting of the superior vena cava and right pulmonary artery in a woman with a mediastinal mass and acute respiratory distress syndrome (ARDS)

We report the case of a woman with a mass in the anterior and middle mediastinum (a non-small-cell lung carcinoma), determining significant compression of both superior vena cava and right pulmonary artery. The patient developed acute respiratory distress syndrome , necessitating intubation and admission to the Intensive Care Unit . Radiotherapy sessions to reduce the mass effect were attempted, without significant clinical improvement. Due to the persistence of severe hypoxemia, stenting of the superior vena cava and the right pulmonary artery was performed, the latter resulting in a significant improvement of the arterial blood gas parameters, allowing extubation of the patient. In our opinion, stenting of the superior vena cava and the pulmonary artery (or its branches) is an effective and safe treatment; it should be considered in similar cases, especially if other - less invasive - treatments fail.     

A correlation between the severity of lung lesions on radiographs and clinical findings in patients with severe acute respiratory syndrome.

OBJECTIVE: The purpose of this study was to quantify lesions on chest radiographs in patients with severe acute respiratory syndrome (SARS) and analyze the severity of the lesions with clinical parameters. MATERIALS AND METHODS: Two experienced radiologists reviewed chest radiographs of 28 patients with SARS. Each lung was divided into upper, middle, and lower zones. A SARS-related lesion in each zone was scored using a four-point scale: zero to three. The mean and maximal radiographic scores were analyzed statistically to determine if the scorings were related to the laboratory data and clinical course. RESULTS: Forward stepwise multiple linear regression showed that the mean radiographic score correlated most significantly with the number of hospitalized days (p < 0.001). The second most significant factor was the absolute lymphocyte count (p < 0.001) and the third most significant factor was the number of days of intubation (p = 0.025). The maximal radiographic score correlated best with the percentage of lymphocytes in a leukocyte count (p < 0.001), while the second most significant factor was the number of hospitalized days (p < 0.001) and the third most significant factor was the absolute lymphocyte count (p = 0.013). The mean radiographic scores of the patients who died, with comorbidities and without a comorbidity were 11.1, 6.3 and 2.9, respectively (p = 0.032). The corresponding value for maximal radiographic scores were 17.7, 9.7 and 6.0, respectively (p = 0.033). CONCLUSION: The severity of abnormalities quantified on chest radiographs in patients with SARS correlates with the clinical parameters.