乌司他丁与沐舒坦治疗严重烧伤伴吸入性损伤的疗效分析

目的:探讨严重烧伤伴中重度吸入性损伤患者早期联合使用大剂量乌司他丁与沐舒坦的临床疗效。方法:选择2003年5月~2013年5月在我院接受治疗的185例严重烧伤伴中重度吸入性损伤患者,随机分为两组,治疗组93例,对照组92例。两组患者在确诊为中重度吸入性损伤后,立即给予传统常规治疗:吸氧、视情尽早预防性气管切开、湿化气道及气道灌洗、翻身拍背吸痰、呼吸机辅助呼吸等。治疗组在常规治疗的基础上给予乌司他丁40万单位,每隔8h静脉滴注,沐舒坦450 mg,每隔12h微泵静推;对照组给予乌司他丁10万单位,每隔8h静滴,沐舒坦30 mg,每隔8h静滴,疗程为10天,比较两组患者急性肺损伤(ALI)的发生率、急性呼吸窘迫综合征(ARDS)的发生率、呼吸机使用时间、死亡率。结果:治疗组93例患者,治愈92例,死亡1例,死亡率为1.08%(1/93),治疗过程中发生ALI34例,ARDS12例,呼吸机使用时间为(4.2±2.1)d。对照组92例患者治愈88例,死亡4例,死亡率率为4.35%(4/92),治疗过程中发生ALI43例,ARDS17例,呼吸机使用时间为(8.2±2.7)d。两组患者ALI发生率、ARDS发生率、呼吸机使用时间、治愈率差异均有统计学意义(P0.05)。结论:对于严重烧伤伴中重度吸入性损伤的患者,在气管切开的前提下,给予常规传统治疗的同时,采用大剂量乌司他丁与沐舒坦早期联合使用给药,能够明显的提高治愈率,降低并发症,值得在临床上广泛推广应用。     

Adult Respiratory Distress Syndrome

Many causes for the adult respiratory distress syndrome (ARDS) have been reported, all with common pathologic, pathophysiologic and biochemical end results. The final common pathway may involve changes in lung content of a critical enzyme, superoxide dismutase, or alterations in surfactant metabolism, or both. The early assumption that the disorder is partially due to oxygen toxicity from inspired oxygen concentrations greater than 60 percent is consistent with findings of recent biochemical studies. Although the lung normally maintains its alveoli dry, during ARDS increased permeability of small pulmonary vessels results in primary pulmonary edema, in contrast to edema from increased vascular pressure. These data have been obtained mainly in animals; whether they apply to humans with ARDS is not certain. Tissue oxygenation is improved by increasing end-expiratory pressure in an animal model of ARDS, more effectively during spontaneous breathing than during mechanical ventilation. During spontaneous breathing, adverse ventilatory effects were caused by stimulation of pulmonary reflexes.     

Acute effects of caffeine and cigarette smoking on ventricular long-axis function in healthy subjects

Background

Differential diagnosis between acute cardiogenic pulmonary edema (APE) and acute lung injury/acute respiratory distress syndrome (ALI/ARDS) may often be difficult. We evaluated the ability of chest sonography in the identification of characteristic pleuropulmonary signs useful in the diagnosis of ALI/ARDS and APE.

Methods

Chest sonography was performed on admission to the intensive care unit in 58 consecutive patients affected by ALI/ARDS or by acute pulmonary edema (APE).

Results

Ultrasound examination was focalised on finding in the two groups the presence of: 1) alveolar-interstitial syndrome (AIS) 2) pleural lines abnormalities 3) absence or reduction of "gliding" sign 4) "spared areas" 5) consolidations 6) pleural effusion 7) "lung pulse". AIS was found in 100% of patients with ALI/ARDS and in 100% of patients with APE (p = ns). Pleural line abnormalities were observed in 100% of patients with ALI/ARDS and in 25% of patients with APE (p < 0.0001). Absence or reduction of the 'gliding sign' was observed in 100% of patients with ALI/ARDS and in 0% of patients with APE. 'Spared areas' were observed in 100% of patients with ALI/ARDS and in 0% of patients with APE (p < 0.0001). Consolidations were present in 83.3% of patients with ALI/ARDS in 0% of patients with APE (p < 0.0001). A pleural effusion was present in 66.6% of patients with ALI/ARDS and in 95% of patients with APE (p < 0.004). 'Lung pulse' was observed in 50% of patients with ALI/ARDS and in 0% of patients with APE (p < 0.0001). All signs, except the presence of AIS, presented a statistically significant difference in presentation between the two syndromes resulting specific for the ultrasonographic characterization of ALI/ARDS.

Conclusion

Pleuroparenchimal patterns in ALI/ARDS do find a characterization through ultrasonographic lung scan. In the critically ill the ultrasound demonstration of a dyshomogeneous AIS with spared areas, pleural line modifications and lung consolidations is strongly predictive, in an early phase, of non-cardiogenic pulmonary edema.     

Vascular endothelial growth factor and related molecules in acute lung injury.

VEGFs and their receptors have been implicated in the regulation of vascular permeability in many organ systems, including the lung. Increased permeability and interstitial and pulmonary edema are prominent features of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Extrapolating data from other organ systems and animal experiments have suggested that overexpression of VEGF functions primarily as proinjurious molecules in the lung. Recent data, from animal models as well as from patients with ARDS, have shown decreased levels of VEGF in the lung. The role of VEGF and related molecules in ALI/ARDS is, therefore, controversial: what has become clear is that there are many unique features in the regulation of pulmonary vascular permeability and in VEGF expression in the lung. In this review, we explore a growing body of literature looking at the expression and function of VEGF and related molecules in different models of ALI and in patients with ALI/ARDS. Novel evidence points to a potential role of VEGF in promoting repair of the alveolar-capillary membrane during recovery from ALI/ARDS. Understanding the role of VEGF in this disease process is crucial for developing new therapeutic strategies for ALI/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。     

乌司他丁对急性肺损伤/急性呼吸窘迫综合征的治疗研究

目的研究大剂量乌司他丁在急性肺损伤/急性呼吸窘迫综合征中的治疗效果。方法回顾性分析2006年1月至2010年1月广西医科大学第一附属医院ICU收治的154例ALI/ARDS患者的临床资料,根据治疗方案分为乌司他丁组(UTI组)(n=80),对照组(n=74)。记录两组患者开始治疗、治疗第3天、治疗第7天的生命体征、动脉血气分析、血生化检查结果;记录患者在ICU治疗的转归。应用SPSS 13.0软件对结果进行统计学分析。结果经治疗3天UTI组呼吸频率低于对照组;动脉血气分析提示两组患者PaO2、PaO2/Fi O2、SaO2均有上升,UTI组PaO2/Fi O2略低于对照组(P0.01),而两组患者PaO2、SaO2比较无统计学差异。UTI组与对照组的死亡率比较(UTI组52.5%,对照组52.7%,P=0.980)无统计学差异,机械通气时间UTI组低于对照组[UTI组(14.8±3.9)天,对照组(16.7±4.2)天,P=0.020]。根据ALI/ARDS发生的病因分为肺内源性及肺外源性进行亚组分析(A组:肺内源性ALI/ARDS,使用UTI治疗;B组:肺内源性ALI/ARDS,不使用UTI治疗;C组:肺外源性ALI/ARDS,使用UTI治疗;D组:肺外源性ALI/ARDS,不使用UTI治疗),发现乌司他丁对肺外源性ALI/ARDS患者(C组)的ICU时间、ICU内死亡率及机械通气时间均低于不使用UTI的患者(D组)。结论大剂量乌司他丁用于ALI/ARDS的临床治疗可有效改善患者氧合指数,减少机械通气时间,且高血糖的发生率低,尤其是乌司他丁治疗肺外源性ALI/ARDS患者的预后优于肺内源性的ALI/ARDS。     

Posttraumatische Belastungsstörung nach ARDS und septischem Schock

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) define medical conditions of acute respiratory insufficiency deriving from direct and indirect damage of the alveolar parenchyma and often associated with multiorgan dysfunction (MODS). As a rule, intensive care is based on mechanical ventilation often requiring high doses of sedatives and narcotics. Despite major progress in intensive care medicine the rate of mortality is still very high. Whereas in the past the level of medical progress has been rated based on the mortality rate alone, the many negative somatic and psychological sequelae in long-term-survivors of ARDS are only now being appreciated. From a perspective of C/L psychiatry persisting cognitive dysfunctions, anxiety and mood disorders, posttraumatic stress disorders (PTSD) in their negative impact on health-related quality of life are intensively investigated. In the etiopathogenesis of PTSD associated with ALI/ARDS, many influences have to be discussed, e.g., increases in CO₂ triggering panic affects, a mismatch of norepinephric overstimulation and cortisol insufficiency, negative effects of high doses of benzodiazepines resulting in oversedation, prolonged phases of weaning and more frequent states of delirium. Consolidation and retrieval of traumatic memories of the ICU stay are influenced by complex factors. From a clinical point of view prophylactic stress doses of hydrocortisone may reduce the major risk of PTSD associated with ALI / ARDS.     

ALI/ARDS患者使用保护性通气策略对于肺部损伤的影响

急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)是常见的临床综合征,绝大多数ALI/ARDS患者需机械通气治疗,机械通气在提供可接受的肺部气体交换的同时治疗基础疾病,但机械通气本身也会引起肺部损伤,即机械通气性肺损伤(VILI)。而通过调整机械通气参数的设置,使用保护性通气策略可显著减低ALI/ARDS患者机械通气性肺损伤程度,从而减少肺部感染,缩短机械通气时间和住院时间,降低28天死亡率,明显改善ALI/ARDS患者的生存质量,起到最大程度地肺保护作用。本文从气道平台压,通气容积,呼气末正压等几个不同通气参数方面分别进行综述,讨论ALI/ARDS患者机械通气时使用保护性通气策略对于肺部损伤的影响。     

Low Testosterone Levels are Frequent in Patients with Acute Respiratory Failure and Are Associated with Poor Outcomes

ObjectiveLow testosterone level is a common finding in critically ill patients with trauma, shock, and sepsis. However, its prevalence and outcomes in patients with primary acute respiratory failure is unknown; low testosterone could contribute to respiratory muscle weakness and further compromise ventilation in these patients.MethodsWe aimed to determine the prevalence, severity, and effects of hypotestosteronemia in patients with acute respiratory failure in a 16-bed single academic center medical intensive care unit (ICU). We studied 30 men who required mechanical ventilation for ≥ 24 hours for a primary diagnosis of acute respiratory failure. Blood samples were drawn on ICU day 1 and day 3 to measure serum levels of total and free testosterone.ResultsHypotestosteronemia (level below the lower reference limit) was present on day 1 in 93.1% (total testosterone) and 76.7% (free testosterone) of patients and on day 3 in 94.4% (total testosterone) and 100% (free testosterone) of patients. Sex hormone–binding globulin, dehydroepiandrosterone sulfate, follicle-stimulating hormone, luteinizing hormone, and thyroid function levels were all within stated reference ranges. Total and free testosterone levels correlated inversely with ventilator days and ICU length of stay.ConclusionHypotestosteronemia is common in mechanically ventilated patients with primary acute respiratory failure and may contribute to longer ICU stay. Further studies are needed to determine the effect of testosterone replacement on short- and long-term outcomes in these patients. (Endocr Pract. 2014;20:1057-1063)     

Curcumin Modulates the Inflammatory Response and Inhibits Subsequent Fibrosis in a Mouse Model of Viral-induced Acute Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or non-infectious insult often leading to the development of intra-alveolar and interstitial fibrosis. Curcumin, the principal curcumoid of the popular Indian spice turmeric, has been demonstrated as an anti-oxidant and anti-inflammatory agent in a broad spectrum of diseases. Using our well-established model of reovirus 1/L-induced acute viral pneumonia, which displays many of the characteristics of the human ALI/ARDS, we evaluated the anti-inflammatory and anti-fibrotic effects of curcumin. Female CBA/J mice were treated with curcumin (50 mg/kg) 5 days prior to intranasal inoculation with 10⁷ pfu reovirus 1/L and daily, thereafter. Mice were evaluated for key features associated with ALI/ARDS. Administration of curcumin significantly modulated inflammation and fibrosis, as revealed by histological and biochemical analysis. The expression of IL-6, IL-10, IFNγ, and MCP-1, key chemokines/cytokines implicated in the development of ALI/ARDS, from both the inflammatory infiltrate and whole lung tissue were modulated by curcumin potentially through a reduction in the phosphorylated form of NFκB p65. While the expression of TGFß1 was not modulated by curcumin, TGFß Receptor II, which is required for TGFß signaling, was significantly reduced. In addition, curcumin also significantly inhibited the expression of α-smooth muscle actin and Tenascin-C, key markers of myofibroblast activation. This data strongly supports a role for curcumin in modulating the pathogenesis of viral-induced ALI/ARDS in a pre-clinical model potentially manifested through the alteration of inflammation and myofibroblast differentiation.     

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 72 h 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 24 h 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.     

黄磷及其化合物急性吸入致大鼠急性肺损伤或急性呼吸窘迫综合征模型的制作

目的建立黄磷及其化合物急性吸入致大鼠急性肺损伤（ALI）/急性呼吸窘迫综合征（ARDS）的模型。方法健康SD大鼠48只随机分为对照组以及实验组（0、4、12、24、48 h时间点处死）。采用自制染毒装置,间歇染毒形成ALI/ARDS模型。观察ALI/ARDS大鼠动脉血气分析以及肺系数和肺组织病理变化。结果肺损伤后大鼠动脉血气分析以及肺组织病理改变明显恶化,肺系数较对照组明显增大。结论成功地建立了黄磷及其化合物急性吸入致大鼠ALI/ARDS的模型,为黄磷及其化合物吸入中毒的防治研究提供良好实验基础,同时也适用于其他气体吸入致ARDS的实验研究。     

Early intravenous unfractionated heparin and outcome in acute lung injury and acute respiratory distress syndrome -- a retrospective propensity matched cohort study

ABSTRACT: BACKGROUND: Acute lung injury (ALI) is characterized by a pro-coagulant state. Heparin is an anticoagulant with anti-inflammatory properties. Unfractionated heparin has been found to be protective in experimental models of ALI. We hypothesized that an intravenous therapeutic dose of unfractionated heparin would favorably influence outcome of critically ill patients diagnosed with ALI. METHODS: Patients admitted to the Intensive Care Unit (ICU) of a tertiary referral center in the Netherlands between November 2004 and October 2007 were screened. Patients who developed ALI (consensus definition) were included. In this cohort, the impact of heparin use on mortality was assessed by logistic regression analysis in a propensity matched case--control design. RESULTS: Of 5,561 admitted patients, 2,138 patients had a length of stay > 48 hours, of whom 723 were diagnosed with ALI (34 %), of whom 164 received intravenous heparin. In a propensity score adjusted logistic regression analysis, heparin use did not influence 28-day mortality (odds ratio 1.23 [confidence interval 95 % 0.80--1.89], nor did it affect ICU length of stay. CONCLUSIONS: Administration of therapeutic doses of intravenous unfractionated heparin was not associated with reduced mortality in critically ill patients diagnosed with ALI. Heparin treatment did not increase transfusion requirements. These results may help in the design of prospective trials evaluating the use of heparin as adjunctive treatment for ALI.     

Mesenchymal stem cells in acute lung injury: are they ready for translational medicine?

Acute lung injury (ALI) is a severe clinical condition responsible for high mortality and the development of multiple organ dysfunctions, because of the lack of specific and effective therapies for ALI. Increasing evidence from pre‐clinical studies supports preventive and therapeutic effects of mesenchymal stem cells (MSCs, also called mesenchymal stromal cells) in ALI/ARDS (acute respiratory distress syndrome). Therapeutic effects of MSCs were noticed in various delivery approaches (systemic, local, or other locations), multiple origins (bone marrow or other tissues), or different schedules of administrations (before or after the challenges). MSCs could reduce the over‐production of inflammatory mediators, leucocyte infiltration, tissue injury and pulmonary failure, and produce a number of benefit factors through interaction with other cells in the process of lung tissue repair. Thus, it is necessary to establish guidelines, standard operating procedures and evaluation criteria for translating MSC‐based therapies into clinical application for patients with ALI.     

Anti-IL-8 autoantibody:IL-8 immune complexes suppress spontaneous apoptosis of neutrophils

Our previous studies demonstrated that a significant fraction of interleukin-8 (IL-8) in lung fluids from patients with acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) is associated with anti-IL-8 autoantibodies (anti-IL-8:IL-8 immune complexes). Neutrophils have been implicated in the pathogenesis of ALI/ARDS, and moreover, it is well-established that apoptosis of neutrophils is delayed in patients with ALI/ARDS. The aim of this study was, therefore, to examine the role of anti-IL-8:IL-8 immune complexes in modulating spontaneous apoptosis of normal human neutrophils. Apoptosis was assessed by evaluating morphological changes, measuring enzymatic activity of caspase-3, and determining the extent of DNA degradation. We found that samples containing anti-IL-8:IL-8 immune complexes but not samples from which these complexes were removed inhibited neutrophil apoptosis. Furthermore, the former samples or effectively anti-IL-8:IL-8 complexes induced an increase in the level of antiapoptotic protein, Bcl-X(L). In contrast, levels of proapoptotic proteins Bax and Bak were decreased in the same conditions. Activity of both caspase-3 and caspase-9 was also suppressed by anti-IL-8:IL-8 complex-containing samples. Finally, we established that IgG receptor, FcgammaRIIa, mediates antiapoptotic activity of anti-IL-8:IL-8 complexes and that the key components of the FcgammaRIIa signaling pathway, Src, Syk, PI3 kinase, and ERK, may be involved in regulation of neutrophil apoptosis by the complexes. These studies demonstrate for the first time that anti-IL-8:IL-8 immune complexes have the ability to prolong neutrophil life.     

Protein C and thrombomodulin in human acute lung injury

Decreased circulating protein C and increased circulating thrombomodulin are markers of the prothrombotic, antifibrinolytic state associated with poor outcomes in sepsis but have not been measured in patients with ALI (acute lung injury)/ARDS (acute respiratory distress syndrome). We measured circulating and intra-alveolar protein C and thrombomodulin in 45 patients with ALI/ARDS from septic and nonseptic causes and correlated the levels with clinical outcomes. Plasma protein C levels were lower in ALI/ARDS compared with normal. Lower levels of protein C were associated with worse clinical outcomes, including death, fewer ventilator-free days, and more nonpulmonary organ failures, even when only patients without sepsis were analyzed. Levels of thrombomodulin in pulmonary edema fluid from ALI/ARDS patients were >10-fold higher than normal plasma and 2-fold higher than ALI/ARDS plasma. Higher edema fluid thrombomodulin levels were associated with worse clinical outcomes. The higher levels in edema fluid compared with plasma suggest local release of soluble thrombomodulin in the lung, possibly from a lung epithelial source. To determine whether lung epithelial cells can release thrombomodulin, A549 cells and primary isolates of human alveolar type II cells were exposed to H2O2 or inflammatory cytokines. Both epithelial cell types released thrombomodulin into the media. In summary, the protein C system is markedly disrupted in patients with ALI/ARDS from both septic and nonseptic causes. The protein C system may be a potential therapeutic target in patients with ALI/ARDS.     

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.     

乌司他丁与沭舒坦治疗严重烧伤伴吸人性损伤的疗效分析

目的：探讨严重烧伤伴中重度吸入性损伤患者早期联合使用大剂量乌司他丁与沐舒坦的临床疗效。方法：选择2003年5月-2013年5月在我院接受治疗的185例严重烧伤伴中重度吸入性损伤患者,随机分为两组,治疗组93例,对照组92例。两组患者在确诊为中重度吸入性损伤后,立即给予传统常规治疗：吸氧、视情尽早预防性气管切开、湿化气道及气道灌洗、翻身拍背吸痰、呼吸机辅助呼吸等。治疗组在常规治疗的基础上给予乌司他丁40万单位,每隔8h静脉滴注,沐舒坦450mg,每隔12h微泵静推;对照组给予乌司他丁10万单位,每隔8h静滴,沐舒坦30mg,每隔8h静滴,疗程为10天,比较两组患者急性肺损伤（Au）的发生率、急性呼吸窘迫综合征（ARDS）的发生率、呼吸机使用时间、死亡率。结果：治疗组93例患者,治愈92例,死亡1例,死亡率为1．08％（1／93）,治疗过程中发生AL134例,ARDS12例,呼吸机使用时间为（4．2±2．1）d。对照组92例患者治愈88例,死亡4例,死亡率率为4．35％（4／92）,治疗过程中发生AL143例,ARDS17例,呼吸机使用时间为（8．2±2．7）d。两组患者ALI发生率、ARDS发生率、呼吸机使用时间、治愈率差异均有统计学意义（P〈0．05）。结论：对于严重烧伤伴中重度吸入性损伤的患者,在气管切开的前提下,给予常规传统治疗的同时,采用大剂量乌司他丁与沐舒坦早期联合使用给药,能够明显的提高治愈率,降低并发症,值得在临床上广泛推广应用。     

Thrombocytopenia Is Associated with Acute Respiratory Distress Syndrome Mortality: An International Study

Background

Early detection of the Acute Respiratory Distress Syndrome (ARDS) has the potential to improvethe prognosis of critically ill patients admitted to the intensive care unit (ICU). However, no reliable biomarkers are currently available for accurate early detection of ARDS in patients with predisposing conditions.

Objectives

This study examined risk factors and biomarkers for ARDS development and mortality in two prospective cohort studies.

Methods

We examined clinical risk factors for ARDS in a cohort of 178 patients in Beijing, China who were admitted to the ICU and were at high risk for ARDS. Identified biomarkers were then replicated in a second cohort of1,878 patients in Boston, USA.

Results

Of 178 patients recruited from participating hospitals in Beijing, 75 developed ARDS. After multivariate adjustment, sepsis (odds ratio [OR]:5.58, 95% CI: 1.70–18.3), pulmonary injury (OR: 3.22; 95% CI: 1.60–6.47), and thrombocytopenia, defined as platelet count <80×10³/µL, (OR: 2.67; 95% CI: 1.27–5.62)were significantly associated with increased risk of developing ARDS. Thrombocytopenia was also associated with increased mortality in patients who developed ARDS (adjusted hazard ratio [AHR]: 1.38, 95% CI: 1.07–1.57) but not in those who did not develop ARDS(AHR: 1.25, 95% CI: 0.96–1.62). The presence of both thrombocytopenia and ARDS substantially increased 60-daymortality. Sensitivity analyses showed that a platelet count of <100×10³/µLin combination with ARDS provide the highest prognostic value for mortality. These associations were replicated in the cohort of US patients.

Conclusions

This study of ICU patients in both China and US showed that thrombocytopenia is associated with an increased risk of ARDS and platelet count in combination with ARDS had a high predictive value for patient mortality.