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聚焦ARDS Neto AS, Dessap AM, Papazian L. Focus on ARDS.Intensive Care Med, 2017, 43(10): 1495-1497.
Since 1967, when first described, ARDS has been widely recognized as a major health problem worldwide, carrying a high morbidity and mortality [1–3]. This focus editorial summarizes recent advances about the incidence, pathophysiology,right ventricular dysfunction, and mortality of ARDS. 1967年首次描述ARDS。这里简述ARDS的发病率、病理生理学、右室功能障碍和病死率。
Despite the attempt to homogenize its definition following the publication of the Berlin criteria,there is still a high heterogeneity in the epidemiology of ARDS across the world [3]. Indeed, estimates of the incidence of ARDS are highly variable,ranging from less than 2 to more than 70 cases per 100,000 person-years, with the most recent study on the topic suggesting a higher incidence in Europe,North America, and Oceania compared to South America, Asia, and Africa [2, 3].However, it is important to emphasize that this scenario could only reflect the under-recognition of this syndrome [3]. 柏林标准试图消除不均一性，但是世界上仍然存在不均一性，流行病学差异很大。最近的流行病学研究发现发病率为2-70/每10万人，欧洲和北美高于南美、亚洲和非洲。但是这可能是由于低估发病率的原因。 Recent reports suggest a progressive decline of the incidence of ARDS. In a study conducted in Rochester, cases fell by half between 2001 and 2008 while mortality remained stable [4]. Nearly all of the reduction in the incidence was observed in hospital-acquired ARDS,suggesting that ARDS could be prevented through strategies addressing its related risk factors [4, 5]. 最近研究也显示2001年和2008年相比，发病率下降了50%，而病死率不变。而发病率的下降几乎均为院内获得性ARDS，提示ARDS可能通过对危险因素的预防而预防。 However, in some instances, patients meeting the Berlin criteria for ARDS lack exposure to common risk factors [6]. It was recently reported that the prevalence of patients with ARDS but without common risk factors was as high as 7.5% [6]. According to medical history, bronchoalveolar lavage fluid cytology, and chest computed tomography (CT) scan patterns, four etiological categories were identified in this group of patients: immune,drug-induced, malignant, and idiopathic [6]. The overall ICU mortality rate was higher in patients lacking common risk factors as compared to their counterparts, even after adjustment for potential confounding factors [6]. 但是有时，符合柏林诊断标准的患者缺乏常见的危险因素。最近研究发现缺乏ARDS常见危险因素的患者发病率高达7.5%。在这组患者中，根据内科病史、支气管灌洗液细胞学和胸部CT表现，将病因分为4种：免疫性、药物相关性、恶性相关，和特发性。即使调整了混杂因素，缺乏常见危险因素的ARDS患者的病死率高于具有常见危险因素的患者。 上面是论述ARDS的发病率。新进展是缺乏ARDS常见危险因素的患者发病率高达7.5%。在这组患者中，根据内科病史、支气管灌洗液细胞学和胸部CT表现，将病因分为4种：免疫性、药物相关性、恶性相关，和特发性。这对既往ARDS的诊断提出了挑战。既往诊断ARDS需要的诊断标准是：具有ARDS的危险因素，急性起病、胸片显示肺部斑片影，和氧合指数的改变。 参考文献 1. Beitler JR,Goligher EC, Schmidt M, et al, ARDSne(x)t Investigators (2016) Personalized medicine for ARDS: the 2035 research agenda. Intensive Care Med 42:756-767 2. Villar J, BlancoJ, Ann JM, et al, ALIEN Network (2011) The ALIEN study: incidence and outcome of acute respiratory distress syndrome in the era of lung protective ventilation.Intensive Care Med 37:1932-1941 3. Bellani G, LaffeyJG, Pham T, et al, LUNG SAFE Investigators, ESICM Trials Group (2016) Epidemiology,patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA 315:788-800 4. Li G, Malinchoc M,Cartin-Ceba R, et al (2011) Eight-year trend of acute respiratory distress syndrome: a population-based study in Olmsted County, Minnesota. Am J RespirCrit Care Med 183:59-66 5. Neto AS, Jaber S(2016) What’s new inmechanical ventilation in patients without ARDS: lessons from the ARDS literature. Intensive Care Med 42:787-789 6. Gibelin A, ParrotA, Maitre B, et al (2016) Acute respiratory distress syndrome mimickers lacking common risk factors of the Berlin definition. Intensive Care Med 42:164-172
It is already well known that ventilator-induced lung injury contributes to ARDS-associated mortality [2, 3]. Recently, some biological markers have been proposed as potential biomarkers of ARDS, such as the soluble form of the receptor for advanced glycation end-products (sRAGE). This biomarker is a trans membrane receptor tha tcan bind multiple ligands resulting in intracellular signaling, leading to activation of the proinflammatory transcription factor nuclear factor κB [7]. Plasma levels of sRAGE could change according to ventilator settings in ARDS patients, as recently suggested by a study describing a significant decrease of sRAGE 1 h after a recruitment maneuver followed by an increase toward baseline values 4 h after the maneuver [7]. It has also been shown that sRAGE is higher in non-survivors than survivors in early pediatric ARDS and strongly correlated with number of non-pulmonary organ failures [8]. 众所周知，呼吸机相关肺损伤促进ARDS的死亡。最近有学者提出ARDS的一些生物标记物，如可溶性糖基化终产物受体（sRAGE）是一种跨膜受体，可与多个配体结合，促进心包内信号转导，导致促炎转录因子NF-κB活化。血浆sRAGE水平与ARDS患者呼吸机设置相关。最近一项研究发现sRAGE水平在肺复张后1h水平下降，在4h后复上升。研究还显示早期小儿ARDS患者中，死亡组sRAGE高于生存组，sRAGE水平与肺外器官功能衰竭相关。 Other biomarkers of endothelial injury are also investigated in ARDS patients. Higher levels ofcirculating endothelial cells were found in the blood of patients with moderate-to-severe ARDS as compared to those with mild or without ARDS [9].Soluble thrombomodulin (sTM) is another biomarker of endothelial injury investigated in ARDS patients [10]. A recent post hoc analysis of a huge cohort showed that higher plasma levels of sTM are associated with increased mortality in ARDS patients [10]. Also, the lack of association between the sTM levels andgenetic variants reported in this latter study suggests that the increased levels of sTM may reflect severity of endothelial damage rather than genetic heterogeneity [10]. Finally, the prognostic value of plasma soluble urokinase plasminogen activator receptor (suPAR) was recently assessed in a series of 632 ARDS patients, and increased levels of plasma suPAR were significantly associated with ICU mortality [11]. 其他内皮损伤的标记物也有研究。与轻度或无ARDS患者相比，中-重度ARDS患者血液中内皮细胞的水平增加。可溶性血栓调节素（sTM）是内皮损伤的另一个标记物。最近研究发现高水平血浆sTM与ARDS病死率增加相关。而且血浆sTM水平与遗传无相关性提示高水平的sTM反应内皮损伤的程度，而不是遗传差异。最后，有研究评价了632例ARDS患者的血浆可溶性尿激酶原激活物受体（suPAR），发现血浆suPAR水平增高的患者病死率增加。 Altogether, these promising endothelial biomarkers may guide the development of future strategies targeting endothelial stabilization, repair, and/or functional replacement incertain ARDS categories. However, their prominent involvement during indirectlung injury likely reflects increased inflammation and both pulmonary and systemic endothelial damage. Indeed, the severity of pulmonary vascular injuryis quite disparate between ARDS patients and may prevail during indirectinjury. 所有这些内皮标记物的研究均提示，未来对于某些ARDS患者的治疗策略是稳定、修复内皮以及恢复内皮的功能。但是，这些主要表现在间接肺损伤患者，提示炎症增加，和肺、全身内皮损伤。确实，ARDS患者肺血管损伤程度有差异，在间接肺损伤时占优势。 上面主要论述ARDS病理生理学，主要提及的是ARDS血液标记物，如跨膜受体（如sRAGE）和内皮损伤标记物。而且研究主要集中与间接肺损伤。 7. Jabaudon M,Hamroun N, Roszyk L, et al (2015) Effects of a recruitment maneuver on plasma levelsof soluble RAGE in patients with diffuse acute respiratory distress syndrome: a prospective randomized crossover study. Intensive Care Med 41:846-855 8. Yehya N, ThomasNJ, Meyer NJ, et al (2016) Circulating markers of endothelial and alveolar epithelial dysfunction are associated with mortality in pediatric acute respiratory distress syndrome. Intensive Care Med 42:1137-1145 9. Moussa MD,Santonocito C, Fagnoul D, et al (2015) Evaluation of endothelial damage in sepsis-related ARDS using circulating endothelial cells. Intensive Care Med 41:231-238 10. Sapru A, CalfeeCS, Liu KD, et al, NHLBI ARDS Network (2015) Plasma soluble thrombomodulin levels are associated with mortality in the acute respiratory distress syndrome. Intensive Care Med 41:470-478 11. Geboers DG, deBeer FM, Tuip-de Boer AM, et al (2015) Plasma suPAR as a prognostic biological marker for ICU mortality in ARDS patients. Intensive Care Med 41:1281-1290
Right ventricular dysfunction may reflect the presence of lung vascular dysfunction during ARDS.In a series of more than 750 patients, the prevalence of acute cor pulmonale during ARDS was found to be 22%, with severe forms being associated with increased mortality [12]. A simple clinical risk score of acute cor pulmonale was proposed, including four variables: pneumonia as a cause of ARDS, driving pressure at least 18 cmH2O, PaO2/FiO2 ratio less than 150 mmHg, and arterial PaCO2at least 48 mmHg [12]. This score may help in selecting patients to be monitored for early identification of acute cor pulmonale, preferably with transesophageal echocardiography [12]. Indeed, recent studies and reviews have reinforced the seminal role of ultrasound in general, and transesophageal echocardiography in particular, in the diagnostic workup and monitoring of ARDS patients [13]. The direct assessment of pulmonary vascular dysfunction at the bedside is still a clinical challenge, but emerging techniques like electric impedance tomography may provide informative data on regional distribution of lung perfusion in the near future [14]. 右室功能不全反应了ARDS患者肺血管功能不全。在一组750例患者中，ARDS患者急性肺心病发病率22%，严重患者与病死率增加相关。有学者提出了包括4个变量在内的急性肺心病危险评分：ARDS的原因是肺感染，驱动压> 18 cmH2O，PaO2/FiO2 <150 mmhg,="" arterial="" paco2=""> 48mmHg。这个评分有助于对可疑急性肺心病患者选择监测如经食管超声检查。最近的研究也强化了超声检查的作用，特别是经食管超声检查在ARDS患者诊断和病情监测中的作用。床旁直接评价肺血管功能不全是一个临床挑战，但是在不久的将来新的技术如电阻抗断层等检查有助于提供局部肺灌注分布的信息。 这部分主要论述ARDS合并右心功能不全的进展。特别是提出了急性肺心病危险评分。以及经食管超声在临床的应用价值。 12. Mekontso DessapA, Boissier F, Charron C, et al (2016) Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: prevalence, predictors,and clinical impact. Intensive Care Med 42:862-870 13. Papazian L,Calfee CS, Chiumello D, et al (2016) Diagnostic workup for ARDS patients. IntensiveCare Med 42:674-685 14. Mauri T, EroniaN, Turrini C, et al (2016) Bedside assessment of the effects of positive end-expiratory pressure on lung inflation and recruitment by the helium dilution technique and electrical impedance tomography. Intensive Care Med 42:1576-1587
The majority of the patients diagnosed with ARDS present it in its moderate form, with an in-hospital mortality rate around 40% [3]. There is a high variability in reported mortality of ARDS patients, probably reflecting differences in care, risk factors, ability to diagnose, and resource availability. However, in general, recent studies suggest a decrease in mortality rate from ARDS probably due to better ventilatory care and control of modifiable risk factors associated with mortality[15]. ARDS在诊断时大多数为中度，院内病死率40%左右。报道ARDS的病死率差异很大，与监护措施、危险因素、诊断能力和资源分布均有关。然而，最近研究发现ARDS的病死率下降，原因可能在于呼吸监护的进展和可改变危险因素的控制。 While we are interested in developing new concepts or techniques to improve mechanical ventilation care or associated measures, we should have in mind that this typeof support cannot cure the patient if the cause of ARDS is not promptly identified and the resulting treatment quickly initiated. This is particularly the case in ARDS related to a direct lung injury which needs a systematic approach based on bronchoalveolar lavage and blood samples to identify the cause of ARDS and to guide the correct treatment [13]. 尽管我们对改进机械通气技术等相关措施感兴趣，我们也应该记住，如果ARDS的病因不能尽快明确并纠正，单纯呼吸支持不能治愈ARDS。因此根据支气管灌洗液和血液标本明确ARDS的病因，特别是间接肺损伤，继而进行正确的治疗是至关重要的。 本部分提示ARDS的病死率仍很高。治疗的关键在于：呼吸支持维护血氧，同时积极寻找和治疗原发病。 15. Laffey JG,Bellani G, Pham T, et al, LUNG SAFE Investigators and the ESICM Trials Group(2016) Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study. Intensive Care Med 42:1865-1876 |
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