Pulmonary mycobacterial infection is associated with increased mortality in patients with acute respiratory distress syndrome

Although pulmonary mycobacterial infection is associated with acute respiratory distress syndrome (ARDS) in critically ill patients, its clinical implication on patients with ARDS has not been clearly elucidated. The aim of study was to investigate the clinical significance of pulmonary mycobacterial infection in patients with ARDS.Between January 2014 and April 2019, medical records of 229 patients with ARDS who met the Berlin criteria and received invasive mechanical ventilation in medical intensive care unit were reviewed. Clinical characteristics and the rate of mortality between patients with and without pulmonary mycobacterial infection were compared. Factors associated with a 28-day mortality were analyzed statistically.Twenty two (9.6%) patients were infected with pulmonary mycobacteria (18 with tuberculosis and 4 with non-tuberculous mycobacteria). There were no differences in baseline characteristics, the severity of illness scores. Other than a higher rate of renal replacement therapy required in those without pulmonary mycobacterial infection, the use of adjunctive therapy did not differ between the groups. The 28- day mortality rate was significantly higher in patients with pulmonary mycobacterial infection (81.8% vs 58%, P = .019). Pulmonary mycobacterial infection was significantly associated with 28-day mortality (hazard ratio 1.852, 95% confidence interval 1.108–3.095, P = .019).Pulmonary mycobacterial infection was associated with increased 28-day mortality in patients with ARDS.     

急性呼吸窘迫综合征患者单核细胞人类白细胞抗原DR表达及其与预后的关系

目的探讨急性呼吸窘迫综合征（ARDS）患者单核细胞人类白细胞抗原DR（HLA-DR）表达及其与预后的关系。方法2004年7月至2005年6月收住东南大学附属中大医院ICU的76例ARDS患者纳入观察。ARDS确诊当天（第1天）及确诊后第7天抽取外周血,应用流式细胞仪检测T淋巴细胞亚群占淋巴细胞百分比、单核细胞HLA-DR表达以及淋巴细胞凋亡。记录患者年龄、性别、导致ARDS的原因,及ARDS确诊当天急性生理和慢性健康（APACHE）Ⅱ评分、心率、呼吸频率、平均动脉压、氧合指数、动脉血pH、动脉血乳酸、外周血血红蛋白浓度、血小板和白细胞计数以及器官功能衰竭个数。以住院28d病死率为预后判定标准。结果与生存组比较,死亡组患者在ARDS第1天和第7天的单核细胞HLA-DR表达均无明显差异。死亡组患者ARDS第7天的单核细胞HLA-DR表达明显低于ARDS第1天。ARDS第1天HLA-DR≤30%的患者生存时间明显低于HLA-DR〉30%患者。ARDS第1天HLA-DR≤30%的患者的28d病死率为67%,有高于HLA-DR〉30%患者（42%）的趋势,但差异无统计学意义。以ARDS第1天HLA-DR≤30%作为判断患者死亡指标,其灵敏度为97%,但特异度仅为17%。以ARDS第1天单核细胞HLA-DR表达判断患者预后的ROC曲线下面积为0.553（P=0.618）,以患者第1天和第7天单核细胞HLA-DR表达变化判断预后的ROC曲线下面积为0.830（P〈0.01）。患者ARDS第1天及第7天HLA-DR表达与APACHEⅡ评分和器官功能衰竭数均无相关性。严重感染导致的ARDS患者的生存时间明显低于其他原因导致的ARDS患者。结论单核细胞HLA-DR≤30%可提示ARDS患者预后不良,HLA-DR表达动态下降对预后判断也具有一定价值。     

Alveolar antioxidant status in patients with acute respiratory distress syndrome.

In the acutely inflamed lung, oxidant stress occurs within the alveolar compartment. Under these conditions, the regulation of low molecular weight antioxidants in the epithelial lining fluid is poorly understood. Therefore, antioxidant levels were measured in the bronchoalveolar lavage fluid (BALF) of patients with acute respiratory distress syndrome (ARDS; n=40) and in healthy volunteers (n=20). Reduced glutathione (GSH), oxidised glutathione (GSSG; enzymatic assay), retinol (vitamin A), alpha-tocopherol (vitamin E), ascorbic acid (vitamin C), uric acid (all by HPLC), plasmalogens (1-alkenyl-2-acyl phospholipids), polyunsaturated fatty acids (PUFA; both by gas-liquid chromatography), and F2-isoprostanes (ELISA) were quantified. All values are expressed as concentrations in cell-depleted BALF. GSSG (ARDS: 0.13+/-0.02 microM; control: 0.03+/-0.01 microM; mean+/-sem) and F2-isoprostanes (ARDS: 78+/-10 pM; control: 26+/-5 pM) were increased in ARDS, thus indicating oxidant stress. GSH levels in patients did not change significantly, whereas concentrations of vitamins A and C, vitamin E (ARDS: 77+/-15 nM; control: 26+/-3 nM) and uric acid (ARDS: 11.8+/-2.2 microM; control: 0.7+/-0.0 microM) were significantly elevated in ARDS. PUFA of total lipids, which may act as sacrificial antioxidants, increased by a factor of approximately 3 in patients, but plasmalogens showed a significant decrease. In conclusion, low molecular weight antioxidants are elevated in the alveolar compartment of patients with acute respiratory distress syndrome. Further research is warranted to elucidate the molecular mechanisms underlying this finding.     

Fluid management in patients with acute respiratory distress syndrome

In a recent review of the data for fluid strategies and ARDS, fluid restriction or diuretic use was graded as "reasonably justifiable by available scientific evidence" and as "strongly supported by expert critical care opinion". Until the ARDS Network trial is published, only general guidelines regarding fluid management with or without specific vascular filling pressures from a pulmonary artery catheter can be made. Ultimately, the rationale for restricting fluid is to reduce hydrostatic pressures as much as possible. It seems most reasonable to maintain the lowest PAOP in ARDS patients that still maintains adequate circulating blood volume, mean arterial perfusion pressures, and cardiac output to provide sufficient oxygen delivery. Other clinical variables such as central venous pressure, urinary output, acid-base status, and lactate, serum urea nitrogen, and serum creatinine levels may help in judging the adequacy of a patient's intravascular volume, especially if central vascular pressure measurements are not available. Measures to reduce total body water, including flood restriction and diuretic use, seem to be of some benefit. Vasopressor use is especially important when systemic perfusion pressures are inadequate to maintain organ blood flow but should not be used to create supranormal levels of oxygen delivery.     

Prone positioning in patients with acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure that is characterized by marked hypoxemia, bilateral infiltrates on chest radiograph, and no clinical evidence of left ventricular failure. Mechanical ventilation with positive end-expiratory pressure (PEEP) is a cornerstone therapy for ARDS patients. Because the fundamental aim of supportive treatment is to improve arterial oxygenation, several alternatives to mechanical ventilation with PEEP have been used. One of these alternative therapies is prone positioning, which has been used safely to improve oxygenation in many patients with ARDS. Despite encouraging results, however, the use of prone positioning is not widely accepted as an adjunct to therapy in hypoxemic patients because, aside from temporarily improving gas exchange, it does not seem to affect the outcome of these patients. This article reviews the rationale for using prone positioning in ARDS patients who require intubation and mechanical ventilation.     

急性呼吸窘迫综合征的肺开放策略

在急性呼吸窘迫综合征患者机械通气中,为了避免小潮气量通气策略所致肺萎陷伤,目前肺开放策略越来越受到重视。本文就肺复张手法及俯卧位通气作一综述,究竟哪一种肺开放策略联合肺保护性通气策略疗效会更好,尚无定论。     

Secretory phospholipase A2-mediated depletion of phosphatidylglycerol in early acute respiratory distress syndrome

IntroductionSecretory phospholipases A₂ (sPLA₂) hydrolyze phospholipids in cell membranes and extracellular structures such as pulmonary surfactant. This study tests the hypothesis that sPLA₂ are elevated in human lungs during acute respiratory distress syndrome (ARDS) and that sPLA₂ levels are associated with surfactant injury by hydrolysis of surfactant phospholipids.MethodsBronchoalveolar lavage (BAL) fluid was obtained from 18 patients with early ARDS (< 72 hours) and compared with samples from 10 healthy volunteers. Secreted phospholipase A₂ levels were measured (enzyme activity and enzyme immunoassay) in conjunction with ARDS subjects’ surfactant abnormalities including surfactant phospholipid composition, large and small aggregates distribution and surface tension function.ResultsBAL sPLA₂ enzyme activity was markedly elevated in ARDS samples relative to healthy subjects when measured by ex vivo hydrolysis of both phosphatidylglycerol (PG) and phosphatidylcholine (PC). Enzyme immunoassay identified increased PLA2G2A protein in the ARDS BAL fluid, which was strongly correlated with the sPLA₂ enzyme activity against PG. Of particular interest, the authors demonstrated an average depletion of 69% of the PG in the ARDS sample large aggregates relative to the normal controls. Furthermore, the sPLA₂ enzyme activity against PG and PC ex vivo correlated with the BAL recovery of in vivo PG and PC, respectively, and also correlated with the altered distribution of the large and small surfactant aggregates.ConclusionsThese results support the hypothesis that sPLA₂-mediated hydrolysis of surfactant phospholipid, especially PG by PLA2G2A, contributes to surfactant injury during early ARDS.     

Partial liquid ventilation in adult patients with acute respiratory distress syndrome

RATIONALE: Despite recent clinical trials demonstrating improved outcome in acute respiratory distress syndrome (ARDS), mortality remains high. Partial liquid ventilation (PLV) using perfluorocarbons has been shown to improve oxygenation and decrease lung injury in various animal models. OBJECTIVE: To determine if PLV would have an impact on outcome in patients with ARDS. METHODS: Patients with ARDS were randomized to (1) conventional mechanical ventilation (CMV; n=107), (2) "low-dose" perfluorocarbon (10 ml/kg; n=99), and (3) "high-dose" perfluorocarbon (20 ml/kg; n=105). Patients in all three groups were ventilated using volume ventilation, Vt or= 0.5, and positive end-expiratory pressure >or= 13 cm H(2)O. RESULTS: The 28-d mortality in the CMV group was 15%, versus 26.3% in the low-dose (p=0.06) and 19.1% in the high-dose (p=0.39) PLV groups. There were more ventilator-free days in the CMV group (13.0+/-9.3) compared with both the low-dose (7.4+/-8.5; p<0.001) and high-dose (9.9+/-9.1; p=0.043) groups. There were more pneumothoraces, hypoxic episodes, and hypotensive episodes in the PLV patients. CONCLUSIONS: PLV at both high and low doses did not improve outcome in ARDS compared with CMV and cannot be recommended for patients with ARDS.     

Deceleration capacity is associated with acute respiratory distress syndrome in COVID-19

BackgroundAcute respiratory distress syndrome (ARDS) is considered the main cause of COVID-19 associated morbidity and mortality. Early and reliable risk stratification is of crucial clinical importance in order to identify persons at risk for developing a severe course of disease. Deceleration capacity (DC) of heart rate as a marker of cardiac autonomic function predicts outcome in persons with myocardial infarction and heart failure. We hypothesized that reduced modulation of heart rate may be helpful in identifying persons with COVID-19 at risk for developing ARDS.MethodsWe prospectively enrolled 60 consecutive COVID-19 positive persons presenting at the University Hospital of Tuebingen. Arterial blood gas analysis and 24 h-Holter ECG recordings were performed and analyzed at admission. The primary end point was defined as development of ARDS with regards to the Berlin classification.Results61.7% (37 of 60 persons) developed an ARDS. In persons with ARDS DC was significantly reduced when compared to persons with milder course of infection (3.2 ms vs. 6.6 ms, p < 0.001). DC achieved a good discrimination performance (AUC = 0.76) for ARDS in COVID-19 persons. In a multivariate analysis, decreased DC was associated with the development of ARDS.ConclusionOur data suggest a promising role of DC to risk stratification in COVID-19.     

Prone position in acute respiratory distress syndrome.

In the last few years prone positioning has been used increasingly in the treatment of patients with acute respiratory distress syndrome (ARDS) and this manoeuvre is now considered a simple and safe method to improve oxygenation. However, the physiological mechanisms causing respiratory function improvement as well as the real clinical benefit are not yet fully understood. The aim of this review is to discuss the physiological and clinical effects of prone positioning in patients with ARDS. The main physiological aims of prone positioning are: 1) to improve oxygenation; 2) to improve respiratory mechanics; 3) to homogenise the pleural pressure gradient, the alveolar inflation and the ventilation distribution; 4) to increase lung volume and reduce the amount of atelectatic regions; 5) to facilitate the drainage of secretions; and 6) to reduce ventilator-associated lung injury. According to the available data, the authors conclude that: 1) oxygenation improves in approximately 70-80% of patients with early acute respiratory distress syndrome; 2) the beneficial effects of oxygenation reduce after 1 week of mechanical ventilation; 3) the aetiology of acute respiratory distress syndrome may markedly affect the response to prone positioning; 4) extreme care is necessary when the manoeuvre is performed; 5) pressure sores are frequent and related to the number of pronations; 6) the supports used to prone and during positioning are different and nonstandardised among centres; and 7) intensive care unit and hospital stay and mortality still remain high despite prone positioning.     

Secretory leukocyte proteinase inhibitor and elafin are resistant to degradation by MMP-8

The naturally occurring neutrophil elastase inhibitors, alpha1-proteinase inhibitor (alpha1PI), secretory leukocyte proteinase inhibitor (SLPI), and elafin, are potential therapeutic agents in the treatment of neutrophil-mediated lung disease. However alpha1PI has been shown to be susceptible to inactivation by matrix metalloproteinases (MMPs) released by neutrophils, particularly neutrophil collagenase (MMP-8). The aim of this study was to determine if SLPI and elafin are similarly susceptible to degradation by this neutrophil-specific MMP. The effect of MMP-8 on SLPI and elafin was assessed by determining the neutrophil elastase inhibitory capacity (NEIC) and electrophoretic protein profile of both inhibitors following exposure to purified MMP-8. As a positive control, the effect of MMP-8 alpha1PI was assessed in parallel. Although treatment of alpha1PI with MMP-8 resulted in a significant decrease in its NEIC (P = .025), no similar decrease was observed with SLPI or elatin. Electrophoretic analysis confirmed digestion of alpha1PI by MMP-8 but no digestion of either SLPI or elafin was observed. These results demonstrate that SLPI and elafin are resistant to proteolytic inactivation by MMP-8, a property that may enhance their therapeutic application in neutrophil-mediated inflammatory lung disease.     

Cyclophosphamide-induced acute respiratory distress syndrome

Cyclophosphamide is widely used in neoplastic and inflammatory diseases. Although several adverse events have been described with its use, acute and subacute interstitial pneumonitis leading to pulmonary fibrosis is rare and potentially fatal. This case report describes a 64-year-old man who, after the fifth chemotherapy cycle, developed a severe ARDS leading to pulmonary fibrosis in just 30 days.     

Sigh in acute respiratory distress syndrome

Mechanical ventilation with plateau pressure lower than 35 cm H2O and high positive end-expiratory pressure (PEEP) has been recommended as lung protective strategy. Ten patients with ARDS (five from pulmonary [p] and five from extrapulmonary [exp] origin), underwent 2 h of lung protective strategy, 1 h of lung protective strategy with three consecutive sighs/min at 45 cm H2O plateau pressure, and 1 h of lung protective strategy. Total minute ventilation, PEEP (14.0 +/- 2.2 cm H2O), inspiratory oxygen fraction, and mean airway pressure were kept constant. After 1 h of sigh we found that: (1) PaO2 increased (from 92.8 +/- 18.6 to 137.6 +/- 23.9 mm Hg, p < 0.01), venous admixture and PaCO2 decreased (from 38 +/- 12 to 28 +/- 14%, p < 0.01; and from 52.7 +/- 19.4 to 49.1 +/- 18.4 mm Hg, p < 0.05, respectively); (2) end-expiratory lung volume increased (from 1.49 +/- 0.58 to 1.91 +/- 0.67 L, p < 0.01), and was significantly correlated with the oxygenation (r = 0.82, p < 0.01) and lung elastance (r = 0.76, p < 0.01) improvement. Sigh was more effective in ARDSexp than in ARDSp. After 1 h of sigh interruption, all the physiologic variables returned to baseline. The derecruitment was correlated with PaCO2 (r = 0.86, p < 0.01). We conclude that: (1) lung protective strategy alone at the PEEP level used in this study may not provide full lung recruitment and best oxygenation; (2) application of sigh during lung protective strategy may improve recruitment and oxygenation.