Angiotensin II formation and endothelin clearance in ARDS patients in supine and prone positions

Objective: In patients with acute respiratory distress syndrome (ARDS), the prone position may enhance oxygenation by changing ventilation/perfusion ratio. In this study, we investigated whether the prone position affects the net balance between pulmonary endothelin (ET-1) and angiotensin II (Ang II) production and clearance, two metabolic functions of lung endothelial cells.¶Setting: Anaesthesiological intensive care unit of a university hospital.¶Patients: Ten ARDS patients (Murray score > 2.5) were studied in both the supine position (SP) and the prone position (PP).¶Measurements and design: Blood samples were taken simultaneously from the patient in SP for assessment of mixed venous and arterial ET-1 and Ang II concentrations, and plasma renin concentration (PRC). This was repeated after 60 min in SP, immediately after turning the patient into PP, and 60 min thereafter. Net arterial/mixed venous ET-1 clearances and net Ang II formations were calculated.¶Results: arterial oxygen tension increased from SP to PP by an average of 60 mmHg, about 20 %. Arterial ET-1 concentrations of ARDS patients were 1.57 ± 1.1 pg/ml (mean ± SD) and within the range of healthy persons. Net ET-1 clearances were negative in SP, indicating pulmonary release of ET-1, and did not change in PP. Arterial Ang II concentrations (73 ± 56 pg/ml) as well as PRC (126 ± 85 pg/ml) were markedly elevated. Net transpulmonary Ang II formation did not change.¶Conclusion: Acute changes of oxygenation in ARDS patients by positioning do not induce any short-term effects on pulmonary ET-1 net clearance or Ang II net formation.     

The role of total static lung compliance in the management of severe ARDS unresponsive to conventional treatment

A group of 36 patients with severe adult respiratory distress syndrome (ARDS) meeting previously established blood gas criteria (mortality rate 90%) became candidates for possible extracorporeal respiratory support [low frequency positive pressure ventilation with extracorporeal CO₂ removal (LFPPV-ECCO₂R)]. Before connecting the patients to bypass we first switched the patients from conventional mechanical ventilation with positive end expiratory pressure (PEEP) to pressure controlled inverted ratio ventilation (PC-IRV), and then when feasible, to spontaneous breathing with continuous positive airways pressure (CPAP). Forty eight hours after the patients had entered the treatment protocol, only 19 out of the 36 patients in fact required LFPPV-ECCO₂R, while 5 were still on PC-IRV, and 12 were on CPAP. The overall mortality rate of the entire population was 23%. The only predictive value of success or failure of a particular treatment mode was total static lung compliance (TSLC). No patients with a TSLC lower than 25 ml (cm H₂O)^-1 tolerated either PC-IRV or CPAP, while all patients with a TSLC higher than 30 ml (cm H₂O)^-1 were successfully treated with CPAP. Borderline patients (TSLC between 25 and 30 ml (cm H₂O)^-1) had to be treated with PC-IRV for more than 48 h, or were then placed on LFPPV-ECCO₂R if Paco₂ rose prohibitively. We conclude that TSLC is a most useful measurement in deciding on the best management of patients with severe ARDS, unresponsive to conventional treatment.     

序贯通气治疗重症急性胰腺炎所致急性呼吸窘迫综合征的随机对照研究

目的：探讨有创-无创序贯通气治疗重症急性胰腺炎所致急性呼吸窘迫综合征（ARDS）的临床疗效。方法选取2012年9月—2014年4月该院收治的108例重症急性胰腺炎所致ARDS患者作为研究对象,采用随机数字表法将所选患者分为研究组和对照组,各54例,研究组采用有创-无创序贯通气治疗,对照组采用有创机械通气治疗,综合比较两组患者有创通气时间、总机械通气时间、住ICU时间、住院费用、呼吸机相关性肺炎(VAP)发生率及病死率。结果研究组有创通气时间、住ICU时间、住院费用均少于对照组（P<0.05）;两组患者总机械通气时间比较差异无统计学意义（P>0.05）;研究组VAP发生率及病死率低于对照组（P<0.05）。结论有创-无创序贯通气治疗重症急性胰腺炎所致ARDS效果确切。     

High lipasemia is frequent in Covid-19 associated acute respiratory distress syndrome

BackgroundCovid-19 is a rapidly spreading viral disease that can cause severe acute respiratory distress syndrome (ARDS). Besides the lungs it can also affect other organs like the heart or the liver. Whether there is a pancreatic manifestation as well is currently unclear.Methodsand aims: We prospectively collected patient information of patients with Covid-19 associated ARDS in a registry (COvid Registry REChts der Isar intensive care Trial – CORRECT) and analyzed this patient cohort for signs of acute pancreatitis (e.g. lipase activity >3 times the upper limit).Results12/38 (31.6%) patients with Covid-19 associated ARDS had a serum lipase activity >180 U/l. Median lipase activity was 422 U/l (186–1127). No patient showed typical findings of acute pancreatitis on imaging studies. On hemodynamic monitoring no patient had signs of intravascular fluid demand regarding MAP, GEDVI and therapy with vasopressors. To avoid worsening respiratory function no treatment with crystalloids was initiated. Lipasemia was not explained by gastroenteritis or renal insufficiency, occurred before as well as after viral clearance and 16.1 ± 6.0 days after the first symptoms. No patient developed severe acute pancreatitis during the follow up period of 35.8 ± 8.3 days.ConclusionHigh lipasemia without typical signs of acute pancreatitis is a frequent finding in severe Covid-19 associated ARDS. Considering the markedly high levels of serum lipase activity, we think impaired microcirculation in severely ill patients can explain this finding rather than extra-pancreatic co-morbidities (UTN: DRKS00021612).     

NOX1 is responsible for cell death through STAT3 activation in hyperoxia and is associated with the pathogenesis of Acute Respiratory Distress Syndrome

Reactive oxygen species (ROS) contribute to alveolar cell death in Acute Respiratory Distress Syndrome (ARDS) and we previously demonstrated that NOX1-derived ROS contributed to hyperoxia-induced alveolar cell death in mice. The study investigates whether NOX1 expression is modulated in epithelial cells concomitantly to cell death and associated to STAT3 signaling in the exudative phase of ARDS. In addition, the role of STAT3 activation in NOX1-dependent epithelial cell death was confirmed by using a lung epithelial cell line and in mice exposed to hyperoxia. NOX1 expression, cell death and STAT3 staining were evaluated in the lungs of control and ARDS patients by immunohistochemistry. In parallel, a stable NOX1-silenced murine epithelial cell line (MLE12) and NOX1-deficient mice were used to characterize signalling pathways. In the present study, we show that NOX1 is detected in alveolar epithelial cells of ARDS patients in the exudative stage. In addition, increased alveolar epithelial cell death and phosphorylated STAT3 are observed in ARDS patients and associated with NOX1 expression. Phosphorylated STAT3 is also correlated with TUNEL staining. We also confirmed that NOX1-dependent STAT3 activation participates to alveolar epithelial cell death. Silencing and acute inhibition of NOX1 in MLE12 led to decreased cell death and cleaved-caspase 3 induced by hyperoxia. Additionally, hyperoxia-induced STAT3 phosphorylation is dependent on NOX1 expression and associated with cell death in MLE12 and mice. This study demonstrates that NOX1 is involved in human ARDS pathophysiology and is responsible for the damage occurring in alveolar epithelial cells at least in part via STAT3 signalling pathways.     

Immunohistochemical expression of MPO,CD163 and VEGF in inflammatory cells in acute respiratory distress syndrome: a case report

Acute respiratory distress syndrome (ARDS) is a serious medical condition occurring in patients with polytrauma, pulmonary or non-pulmonary sepsis, pneumonia and many other circumstances. It causes inflammation of the lung parenchyma leading to impaired gas exchange with a systemic release of inflammatory mediators, causing consequential lung tissue injury, hypoxemia and frequently multiple organ failure. The aim of current study was to describe expression of inflammatory markers (myeloperoxidase, CD163 and vascular endothelial growth factor) by the cells in acute phase of ARDS. The lung samples of a 20-year-old man who had suffered a serious motorbike accident were obtained for histological examination. He died on the seventh day as a consequence of respiratory failure. Our results imply that expression of CD163 was restricted to activated alveolar macrophages and monocytes. Immunopositivityof MPO was observed in neutrophil granulocytes within lung alveoli and lung blood vessels. Myeloperoxidase positivity was observed in alveolar macrophages, too. Vascular endothelial growth factor was expressed in cytoplasm of neutrophil granulocytes, monocytes, small-sized alveolar macrophages and type II pneumocytes localized mostly inside lung alveoli. On the contrary, no positivity was observed in lung endothelial cells of blood vessels.     

Total ginsenosides synergize with ulinastatin against septic acute lung injury and acute respir atory distress syndrome

Total ginsenosides synergize with ulinastatin (UTI) against septic acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We randomly divided 80 cases of severe sepsis-induced ALI and ARDS into a UTI group and a ginsenosides (GS)+UTI group. Continuous electrocardiac monitoring of pulse, respiratory rate, blood pressure, and heart rate; invasive hemodynamic monitoring; ventilator-assisted breathing and circulation support; and anti-infection as well as UTI treatment were given in the UTI group with GS treatment added for 7 consecutive days in the GS+UTI group. The indicators of pulmonary vascular permeability, pulmonary circulation, blood gases, and hemodynamics as well as APACHE II and ALI scores were detected on days 1, 3, and 7. The ALI score in the GS+UTI group was significantly decreased (P < 0.05) compared with that of the UTI group, and the indicators of pulmonary capillary permeability such as pulmonary vascular permeability index, extravascular lung water index, and oxygenation index, in the GS+UTI group improved significantly more than that of the UTI group. The indicators of hemodynamics and pulmonary circulation such as cardiac index, intrathoracic blood volume index, and central venous pressure improved significantly (P < 0.05), and the APACHE II score in the GS+UTI group was lower than that of the UTI group. GS can effectively collaborate with UTI against ALI and/or ARDS.     

俯卧位通气治疗肺内/外源性ARDS的对比研究

目的探讨俯卧位通气下肺内/外源性急性呼吸窘迫综合征(ARDS)患者的疗效及预后。方法对36例ARDS患者按不同发病原因分为肺内源性组及肺外源性组。两组均实施俯卧位通气治疗,每次治疗时间均为4 h。分别记录两组患者通气前及通气后1 h、2 h、4 h时的气道峰压(Pip)、气道平台压(Pplat)、静态肺顺应性(Cst)、气道阻力(Raw)、平均动脉压(MAP)、心率(HR)、心指数(CI)等指标,并进行血气分析检查记录动脉血氧分压(Pa O2)、氧合指数(Pa O2/Fi O2)、动脉血二氧化碳分压(Pa CO2)、动脉血氧饱和度(Sa O2)。结果肺内源性组患者俯卧位通气1 h、2 h后Pa O2/Fi O2、Pa CO2、Pa O2较通气前无明显改善(P0.05),4 h较前有显著性改善(P0.05)。肺外源性组1 h即开始改善(P0.05),2 h较1 h改善更显著(P0.05),4 h较2 h上述指标改善有所下降。肺外源性组患者各项氧合指标在2 h改善优于肺内源性组患者(P0.05),在4 h与肺内源性组差异无显著性(P0.05)。两组患者俯卧位通气后较前在Pip、Pplat、Cst、Raw、HR、MAP、CI等参数上的变化差异无显著性(P0.05),肺外源性组与肺内源性组差异无显著性(P0.05)。结论俯卧位通气可改善肺内/外源性ARDS患者的氧合状况。肺外源性ARDS俯卧位通气早期氧合改善效果优于肺内源性组,且较肺内源性组氧合改善迅速,但维持时间短。肺内源性组ARDS氧合改善较肺外源性所需时间长。俯卧位通气治疗对其呼吸力学以及血流动力学指标无显著影响。     

Granulocyte colony‐stimulating factor‐producing lung cancer and acute respiratory distress syndrome

Granulocyte colony‐stimulating factor (G‐CSF)‐producing lung cancers are known to cause extreme leukocytosis. However, acute respiratory distress syndrome (ARDS) caused by G‐CSF‐producing lung cancer is extremely rare. We present a case of G‐CSF‐producing lung cancer with marked leukocytosis, which rapidly led to severe ARDS after the patient developed pneumonia. The present case suggests that extreme leukocytosis may easily lead to ARDS, triggered by infection. Thus, G‐CSF‐producing lung cancer with marked leukocytosis should be carefully monitored before surgery and during treatment.