Screening of ARDS patients using standardized ventilator settings: influence on enrollment in a clinical trial

Objectives The American–European consensus conference (AECC) definition for acute respiratory distress syndrome (ARDS) requires a PaO₂/F_IO₂200 mmHg, regardless of ventilator settings. We report the results of using standardized ventilator settings to screen and enroll ARDS patients in a clinical trial of high-frequency oscillatory ventilation (HFOV), including the impact on study enrollment, and potential effects on study outcome.Design Prospective cohort study.Setting Intensive care units in two teaching hospitals.Participants A consecutive sample of 41 patients with early ARDS by AECC criteria (baseline PaO₂/F_IO₂200) who met all other inclusion/exclusion criteria for the HFOV trial.Interventions Patients were placed on standardized ventilator settings (tidal volume 7–8 ml/kg, PEEP 10 cmH₂O, F_IO₂ 1.0), and the PaO₂/F_IO₂ was reassessed after 30 min.Results Seventeen patients (41.5%) had PaO₂/F_IO₂ ratios that remained 200 mmHg [Persistent ARDS; PaO₂/F_IO₂=94±36 (mean±SD)] and went on to inclusion in the HFOV study; however, in 24 patients (58.5%) the PaO₂/F_IO₂ was >200 mmHg [Transient ARDS; PaO₂/F_IO₂=310±74] and these patients were ineligible for the HFOV study. The ICU mortality was significantly greater (52.9 vs 12.5%; p=0.01) in the Persistent ARDS patients.Conclusions The use of these standardized ventilatory significantly impacted the PaO₂/F_IO₂ ratio and therefore the ARDS prevalence and trial enrollment. These results have effects on the evaluation of the current ARDS literature and conduct of clinical trials in ARDS and hence consideration should be given to the use of standardized ventilatory settings in future ARDS trials.Electronic Supplementary Material Supplementary Material is available in the online version of this article at     

ARDS after accidental inhalation of zinc chloride smoke

Five soldiers were injured by inhalation of hexite smoke (ZnCl₂) during military training. Two soldiers, not wearing gas masks breathed hexite for 1 or 2 min, they slowly developed severe adult respiratory distress syndrome (ARDS) over the ensuing 2 weeks. This slow, progressive clinical course has not been previously described. In both patients, an increased plasma zinc concentration was measured 3 weeks after the incident. Intravenous and nebulized acetylcysteine increased the urinary excretion of zinc, and briefly decreased the plasma levels. In an attempt to arrest collagen deposition in the lungs, L-3,4 dehydroproline was administered. Both patients died of severe respiratory failure (25 and 32 days after inhalation). At autopsy diffuse microvascular obliteration, widespread occulusion of the pulmonary arteries and extensive interstitial and intra-alveolar fibrosis was observed. Three soldiers wearing ill fitting gas masks, immediately developed severe coughing and dyspnea. They improved, and 12 months after exposure their lung function tests were nearly normal, but they still had slight dyspnea on exercise.     

N-乙酰半胱氨酸对急性呼吸窘迫综合征肺纤维化的抑制作用

目的 从细胞水平观察N-乙酰半胱氨酸(NAC)对脂多糖(LPS)诱导氧自由基损伤致急性呼吸窘迫综合征(ARDS)肺纤维化形成的影响.方法 体外培养人胚肺成纤维细胞,分为空白对照组、LPS刺激组、NAC处理组、地塞米松(DEX)处理对照组4组,分别加入不含处理因素的培养液及含有LPS(1μg/ml)、NAC(1 mmol/L) +LPS(1μg/ml)、DEX(1μmol/L)+LPS(1 μg/ml)的培养液.培养24 h后测定细胞内胶原蛋白和还原型谷胱甘肽(GSH)的含量,以评价各因素对肺纤维化的影响.结果 与空白对照组比较,LPS刺激组肺成纤维细胞中胶原蛋白含量(μg/mg)显著增加(78.97±1.79比72.90±1.70,P＜0.05),GSH含量(μg／mg)显著减少(23.27土0.92比26.34±0.83,P＜0.05);NAC与DEX均可明显抑制LPS的作用(胶原蛋白含量:72.23±1.35、73.64±1.89比78.97±1.79;GSH含量:26.52±0.62、25.85±0.60比23.27±0.92,P＜0.05或P＜0.01);NAC与DEX的作用无差异.结论 NAC可抑制氧自由基损伤及ARDS肺纤维化.     

密闭式吸痰在成人呼吸窘迫综合征患者机械通气中的应用

目的:探讨密闭式吸痰对成人呼吸窘迫综合征患者吸痰前后在血氧饱和度、血流动力学、气道黏膜损伤的影响。方法:选取50例在ICU需行机械通气的成人呼吸窘迫综合征患者,将其随机分为对照组和实验组,各25例。对照组采用开放式吸痰,实验组采用密闭式吸痰。监测两组患者吸痰前后血氧饱和度、心率、血压的变化及气道黏膜损伤的情况。结果:两组患者吸痰前1 min SpO2、心率、血压等指标间差异无统计学意义(P0.05)。吸痰后5 min实验组与对照组相比,SpO2明显升高,心率、收缩压明显降低(P0.05,P0.01)。实验组吸痰前、后心率及收缩压有明显下降,两者相比有显著性差异(P0.01)。实验组气道黏膜损伤情况低于对照组(P0.05)。结论:密闭式吸痰能降低患者由吸痰引起的成人呼吸窘迫综合征的血氧水平,维持血流动力学稳定,减轻气道黏膜损伤。     

ARDS Network (NHLBI) studies: successes and challenges in ARDS clinical research

To hasten the development of effective therapy for acute respiratory distress syndrome (ARDS), in 1994, the National Heart, Lung, and Blood Institute initiated a clinical network to carry out multicenter clinical trials of ARDS treatments. The ARDS Network is a clinical research network of?approximately 42 hospitals, organized into 12 clinical sites. The goal of the Network is to efficiently test promising agents, devices, or management strategies to improve the care of patients with ARDS. Comprehensive information regarding all completed and ongoing ARDSNet clinical trials is available at www.ardsnet.org, but a brief summary is provided in this article.     

乌司他丁对ARDS肺血管内皮通透性的临床研究

目的观察乌司他丁对急性呼吸窘迫综合征（ARDS）患者肺血管内皮通透性的变化：方法将54例ARDS患者随机分为治疗组与对照组。两组给予常规综合及机械通气治疗,治疗组在综合治疗的基础上静脉给予乌司他丁：观察两组治疗前后血管外肺水指R（EVLWI）、肺血管通透性指数（PVPI）、急性生理和慢性健康状态评分（APACHE）Ⅱ、全身性感染相关性器官功能衰竭评分（SOFA）等的变化,评价机械通气时间、ICU住院时间与病死率的差异。结果治疗组EVLWI、PaO2/FiO2、APACHEⅡ评分在治疗后3d、7d与对照组比较,差异均有统计学意义（t分别=2．27、2．86、3．91、5．34、2．52、3．23,P均〈0．05）;PVPI、SOFA评分在治疗后7d与对照组比较,差异有统计学意义（t分别=5．02、2．25,P均〈0．05）。治疗后治疗组的机械通气时间、ICU住院时间明显缩短,与对照组比较,差异均有统计学意义（t分别=3．39、3．58,P均〈0．05）;两组患者28d死亡率比较,差异无统计学意义（x^2=0．38,P〉0．05）。结论乌司他丁能增加氧合,改善ARDS患者肺血管通透性,减少机械通气时间及ICU住院时间．     

High-frequency oscillatory ventilation in ALI/ARDS

In the last 2 decades, our goals for mechanical ventilatory support in patients with acute respiratory distress syndrome (ARDS) or acute lung injury (ALI) have changed dramatically. Several randomized controlled trials have built on a substantial body of preclinical work to demonstrate that the way in which we employ mechanical ventilation has an impact on important patient outcomes. Avoiding ventilator-induced lung injury (VILI) is now a major focus when clinicians are considering which ventilatory strategy to employ in patients with ALI/ARDS. Physicians are searching for methods that may further limit VILI, while still achieving adequate gas exchange.     

连续性静脉-静脉血液滤过联合机械通气治疗ARDS的临床观察

目的　观察连续性静脉 -静脉血液滤过 (CVVH)联合机械通气治疗ARDS患者的临床疗效。方法　选择入住ICU符合ARDS诊断标准的患者 4 0例 ,随机分为 2组 :A组 2 1例 ,采用常规治疗 +机械通气 ;B组 1 9例 ,采用常规治疗 +机械通气 +CVVH。分别观察 2组患者在使用呼吸机时间、氧合指数、吸入氧浓度、动脉血氧分压、PEEP水平、心率、血压及病死率等方面的差别。结果　A、B两组患者在病因、年龄、性别、APACHEⅡ评分及平均脏器功能障碍数等方面相似 ,B组患者加用CVVH后 ,各项指标经统计学处理显示 :病死率 ,B组与A组比较 ,差异有显著性意义 (P <0 0 5 ) :其他指标与A组比较 ,差异均有高度显著性意义 (P <0 0 1 )。结论　CVVH疗法可有效清除ARDS患者血管外肺水和各种应激激素、致炎介质 ,明显改善了ARDS患者肺部氧合功能及血流动力学指标 ,提高了抢救成功率     

ARDS in patients with thermal injury

Objective: To determine the time to onset of the adult respiratory distress syndrome (ARDS) in patients with thermal injury requiring mechanical ventilation. Secondarily, to consider the burn-related risk factors, demographics, incidence, and mortality for ARDS in this population.¶Design: Retrospective chart review; ARDS defined according to the American-European Consensus Conference and the Lung Injury Severity Score definitions.¶Setting: Regional, tertiary referral, adult burn unit in a university teaching hospital.¶Patients and participants: Patients with thermal injury requiring mechanical ventilation, admitted between 1 January 1991 and 28 February 1995.¶Interventions: None.¶Measurements and results: Of 469 consecutive admissions, 126 (26.9 %) received intubation and mechanical ventilation. ARDS was defined according to the American-European Consensus and Lung Injury Severity Score (score > 2.5) definitions. The mean time to onset of ARDS from admission to the burn unit was 6.9 ± 5.2 and 8.2 ± 10.7 days when defined by the American-European Consensus and Lung Injury Severity Score definitions respectively (p = 0.41). Of the intubated patients, 53.6 and 45.2 % developed ARDS according to the American-European Consensus and Lung Injury Severity Score definitions, respectively (p = 0.19). Using multivariate logistic analysis, only age proved to be an independent risk factor for the development of ARDS (p = 0.03), although there was a trend toward an increased incidence of inhalation injury in patients with ARDS. Mortality was not significantly greater (41.8 vs 32.2 %) in those with ARDS compared to those without (p = 0.27).¶Conclusions: According to the American-European Consensus Conference and the Lung Injury Severity Score definitions, ARDS is common in the adult burn population and has a delayed onset compared to most critical care populations. We found age to be a major predisposing factor for ARDS.     

HA-1A in septic patients with ARDS: Results from the pivotal trial

Objective To evaluate the effects of HA-1A, a human monoclonal antiendotoxin antibody, in septic patients with ARDS.Design Substudy of a multicenter, double-blinded, placebo-controlled trial of HA-1A in septic patients.Patients 63 septic patients with ARDS at the time of study entry.Intervention A single intravenous injection of HA-1A (100 mg) or placebo.Results A quantitative radiographic score, the PaO₂/FIO₂ ratio and an index of the severity of ARDS did not show a significant difference between the treatment and placebo groups at 3, 5 and 7 days after treatment. The duration of endotracheal intubation did not differ between the two groups. 15 of 30 HA-1A treated patients (50%) and 23 of 33 placebo-treated patients (69.7%) died within 28 days. The daily mortality was always lower in the HA-1A group, but this difference was not statistically significant at 28 days. The 28-day survival curves for the two treatment groups adjusted by covariate analysis were not significantly different (p=0.07). Using logistic regression, a significant independent effect of HA-1A treatment was detected upon the early survival rate at 7 days (p=0.03) but not at 14 and 28 days.Conclusion A single injection of HA-1A in septic patients with ARDS did not reverse acute respiratory failure or improve long-term survival.This study was supported by a grant from Centocor Inc., Malvern, PA, USA     

Improved determination of static compliance by automated single volume steps in ventilated patients

A new method for determination the static compliance of the respiratory system is described (static compliance by automated single steps-SCASS). In 12 ventilated patients pressure/volume (P/V) curves were determined by automated repetitive occlusion (6 s) at single volume steps and compared to the conventional syringe method (SM). All measurements were corrected for effects of temperature, humidity and pressure (THP). SM was found to be significantly influenced by intrapulmonary gas exchange causing an effective mean volume deficit of 217.4±65.7 ml (BTPS) at the end of the deflation. In contrast to that, the short duration of occlusion in SCASS minimize the gas exchange effects. The methodical differences between both methods result in overestimation of the inflation compliance in the uncorrected SM (SM_uncorr: 83.4±12.6; SCASS: 76.0±11.9 ml/cmH₂O.p<0.01) and underestimation of the deflation compliance resp. (SM_uncorr: 58.3±7.5; SCASS: 79.1±15.0 ml/cmH₂O.p<0.005). In contrast to the P/V curves by SM no significant hysteresis was found by SCASS. Gas exchange seems to be the main reason for the hysteresis. Even after correcting gas exchange and THP effects a significant hyseresis remained. The SCASS method avoids these problems and allows furthermore an accurate checking of leaks.     

FDG-PET in patients at risk for acute respiratory distress syndrome: a preliminary report

Objective  To compare the pattern of lung uptake of 18F-fluorodeoxyglucose (FDG) by positron emission tomography (PET) imaging in patients with lung contusion that developed or did not progress to acute respiratory distress syndrome (ARDS). Design  Prospective, observational study. Setting  Trauma Center (academic urban hospital). Patients and interventions  Eight patients with blunt thoracic trauma and pulmonary contusion, confirmed by computed tomography (CT) on admission, underwent repeat CT and FDG-PET (on the same day) 24–72 h after admission. Results  No subjects met the criteria for ARDS at the time of the PET and second CT. Four subjects subsequently developed ARDS 1–3 days after the PET scan; the other four did not develop the syndrome. Three of the four subjects who subsequently developed ARDS showed diffuse FDG uptake throughout the entire lungs, while those who did not develop ARDS showed significant FDG uptake only in areas of focal lung opacity (non or poorly aerated lung units) on CT. FDG uptake in normally aerated lung regions was higher for those who subsequently developed ARDS than those who did not, approaching statistical significance. The normally aerated tissue:liver ratio was significantly higher in subjects who developed ARDS than in those who did not (P = 0.029). Conclusion  In this small series of patients with thoracic trauma, diffuse lung uptake of FDG was detected by PET imaging 1–3 days prior to clinically determined ARDS. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

The pathology and biology of uremic pneumonitis

Uremic pneumonitis is included in the adult respiratory distress syndrome. Diffuse alveolo-capillary damage, interstitial and intraalveolar edema, widespread atelectases, alveolar haemorrhages and pulmonary hyaline membranes are characteristic but not pathognomonic findigns in uremic pneumonitits. Investigations showed that uremic pneumonitis results from diffuse permeability disorders of the alveolo-capillary permeability combined with an intrarenal or generalized consumption of coagulation factors, and a subsequent state of hypercoagulability. A comparative morphological and clinical analysis of 66 autopsy cases with severe uremia showed that neither the intensity of the urea retention nor the intensity of the creatinine retention correlate with the morphologic symptoms of uremic pneumonitis. Uremia may induce the basic alveolocapillary damage and the subsequent plasmatic leakage into the alveoli and alveolar ducts but uremia has obviously no influence on the simultaneous formation of pulmonary hyaline membranes and intraalveolar bleedings. Hyaline membranes and intraalveolar bleedings are the entire equivalents of the immediate procoagulative activity of the underlying diseases.Dedicated to Professor Dr. Johannes Linzbach, Göttingen, on the occasion of his 70th birthday     

Extracorporeal CO(2) removal in ARDS

Acute respiratory distress syndrome remains one of the most clinically vexing problems in critical care. As technology continues to evolve, it is likely that extracorporeal CO(2) removal devices will become smaller, more efficient, and safer. As the risk of extracorporeal support decreases, devices' role in acute respiratory distress syndrome patients remains to be defined. This article discusses the functional properties and management techniques of CO(2) removal and intracorporeal membrane oxygenation and provides a glimpse into the future of long-term gas-exchange devices.     

Sequential production of leukaemia inhibitory factor by blood cell culture in patients with ARDS

Objective: Leukaemia inhibitory factor (LIF) is a polyfunctional cytokine integrated in cytokine networks and its concentration has been shown to be elevated in bronchoalveolar lavage fluid of patients with the acute respiratory distress syndrome (ARDS). The aim of our study was to evaluate the production of LIF by culturing blood cells from patients with ARDS. Patients: 8 patients with ARDS, 8 patients with pneumonia and 5 healthy subjects. Measurements and results: The blood samples were taken on day 1 after onset of ARDS. LIF was measured, in the cell-free supernatant, with an enzyme-linked immunosorbent assay after 24 h, 48 h and 72 h of blood cell culture. LIF was detectable in some patients in the ARDS group: at i) at 24 h and 48 h: in 2 patients ii) at 72 h in 4/5 patients (140 ± 231 pg/ml). Only in the 4 patients in whom LIF was measured at 72 h was ARDS associated with the multiple organ dysfunction syndrome. Furthermore, among the 5 patients with ARDS who subsequently died, 4 had a detectable LIF. Conclusions: We have observed that LIF was produced only in ARDS, but not in all patients. The production of LIF seems to be a good indicator of the severity of ARDS. These preliminary results must be confirmed by a larger study. Received: 31 July 1997 Accepted: 13 January 1998     

不同肺复张模式对急性呼吸窘迫综合征患者呼吸功能及血管外肺水指数的影响

目的探讨控制性肺膨胀(SI)和压力控制(PCV)两种肺复张(RM)对急性呼吸窘迫综合征(ARDS)患者呼吸力学及血管外肺水指数(EVLWI)的影响。方法采用随机对照病例研究方法,选择30例ARDS患者,随机分为SI组和PCV组,每组15例。SI组:保护性肺通气稳定0.5h后呼吸机模式改为持续正压通气(3.92kPa),持续40s;PCV组:呼吸机模式改为PCV,吸气压力(Pessure above PEEP,1.96kPa),I∶E=1∶1,持续2min。肺复张结束后,2组均恢复呼吸机基础参数。每12h重复1次RM,连续3d。收集2组患者治疗前,治疗12、24、48、72h各时间点氧合指数(PaO2/FiO2)、气道峰压(PIP)、气道平台压(Pplat)、静态肺顺应性(Cst)及EVLWI;监测每次RM前后血流动力学变化。结果 1)治疗后2组患者PaO2/FiO2、Cst均呈上升趋势(P<0.05或P<0.01),PIP、Pplat值在治疗后均呈下降趋势,但在各时间点2组比较差异无统计学意义(P>0.05)。2)治疗后2组EVLWI均呈下降趋势(P<0.01),但各时间点2组比较差异无统计学意义(P>0.05)。3)2组患者在肺复张时平均动脉压、心脏指数下降,心率、中心静脉压升高,与复张前比较差异有统计学意义(P<0.01),PCV组上述指标波动幅度及持续时间均低于SI组,在肺复张时、复张后2min、复张后5min上述指标比较差异有统计学意义(P<0.01)。结论 SI与PCV两种肺复张均能改善肺氧合及肺顺应性,减少ARDS患者EVLWI,PCV肺复张对血流动力学影响低于SI。     

Effects of aprotinin on hemorrhagic complications in ARDS patients during prolonged extracorporeal CO2 removal

The effects of aprotinin, a broad-based proteinase inhibitor, in the management of hemorrhagic complications during prolonged venovenous extracorporeal CO₂ removal in patients with adult respiratory distress syndrome are not evaluated. In two patients, aprotinin infusion was added to heparin to treat bleeding, occurring after few days of bypass and responsible for respiratory and hemodynamic deterioration. After aprotinin infusion (loading dose of 2×10⁶ kIU followed by a continuous infusion of 5×10⁵ kIU/h) combined with heparin, bleeding vanished until the end of bypass.     

Aspirin effect on early and late changes in acute lung injury in sheep

Objective There have been several studies that have already explored the potential beneficial role of cyclo-oxygenase (CO) inhibitors on oleic acid (OA)-induced lung injury in different species. These studies report no significant effect of CO inhibition, though thromboxane B₂ (TxB₂) was effectively blocked. However, recent studies indicate that pre-treatment with aspirin (ASA) preserve gas exchange in OA lung injury in dogs. Aim of our study has been to evaluate the potential beneficial effects of the pre-treatment with low doses of ASA on gas exchange, hemodynamics, respiratory mechanics, prostanoids and lung histology in OA-induced lung injury in sheep.Design 0.09 ml/kg of OA was administered into the right atrium of 14 anaesthetized sheep. Six received a bolus of ASA (10 mg/kg i. v.) 30 min before OA, the others saline as placebo.Measurements and results Pulmonary and tissue gas exchange, pulmonary and systemic hemodynamics, respiratory system mechanics, TxB₂ and 6-keto-PGF1, leukocytes and platelets concentrations were measured throughout the subsequent 3 h and lung histology was effected at end-experiment. The principal findings of our study are: 1) ASA reduces OA-induced early pulmonary vasoconstriction and bronchoconstriction, parallelled by a suppression of TxB₂ generation; 2) the late increase in pulmonary artery pressure and airway resistance due to OA is not inhibited by ASA; 3) the early disturbance in pulmonary gas exchange is reduced by ASA, whereas the late severe deterioration is exaggerated by ASA; 4) the stability of tissue exchange ratio (R) at 1 in ASA-group compared to its fall to 0.7 in controls.Conclusion Our findings suggest that ASA: 1) is only effective to treat the very transient TxB₂-induced pulmonary vasoconstriction resulting in hydrostatic edema, and it is ineffective, even accentuates, the subsequent major pulmonary endothelial cell injury leading to alveolar flooding that is unrelated to TxB₂; 2) has a transient protective effect on the TxB₂-induced early bronchospasm; 3) has a biphasic behaviour on gas exchange, with a benefit which lasts only one hour and then results in a worse gas exchange; 4) has an immediate, stabilizing, persisting effect on R, contrasting with its transient effect on pulmonary hemodynamics and PaO₂.     

急性肺损伤/急性呼吸窘迫综合征中的趋化因子

近年很多研究显示活化的白细胞和趋化因子在ALI/ARDS发病机制中扮演关键角色.临床及实验室研究发现越来越多的天然或合成物通过趋化因子途径对ALI/ARDS产生干预,有些干预对ALI/ARDS可能是有效的.本文就此作一综述.     

血管外肺水指标在脓毒症合并急性肺损伤/急性呼吸窘迫综合征患者中的作用

目的 应用PiCCO技术监测并比较脓毒症合并急性肺损伤(ALI)或急性呼吸窘迫综合征(ARDS)患者的血流动力学改变,以探讨血管外肺水与各肺损伤指标及肺内炎症因子水平的相关性.方法 选取40例2009年至2010年广州市第一人民医院ICU住院脓毒症患者进行观察,其中未合并ALI/ARDS的患者作为对照组.应用PiCCO技术连续7d监测血管外肺水等血流动力学指标,并记录血气分析结果、呼吸机参数、胸片,检测血清及肺泡灌洗液中炎症因子白介素-1( IL-1)及肿瘤坏死因子-α(TNF-α)的水平.结果 在40例脓毒症患者中,15例(37.5％)合并ARDS,14例(35％)合并ALI.与对照组相比,ALI及ARDS患者表现为显著增高的血管外肺水指数(EVLWI)及肺泡灌洗液中IL-1、TNF-α水平.同时,血管外肺水指数与氧合指数、肺损伤指数及IL-1、TNF-α水平呈显著相关性(r=-0.524,r=0.147,r=0.572,r=0.655;P＜0.05),且高ELVW水平组患者ICU病死率及住院病死率均显著高于低ELVW水平组.结论 在脓毒症介导的ALI及ARDS患者中,血管外肺水指标与肺内炎症因子水平及肺损伤严重程度具有相关性.因此,EVLW的检测可能对于判断脓毒症患者肺损伤程度及预后具有一定意义.