JAMA: ARDS新分类以缺氧严重程度为准

旧金山(EGMN)——在美国胸科学会国际会议上提出的急性呼吸窘迫综合征(ARDS)新定义根据轻度、中度和重度缺氧来分类，提示缺氧越严重，病死率就越高，幸存者接受机械通气的时间也越长。轻度、中度和重度ARDS患者的死亡风险分别为27%、32%和45%，幸存者接受机械通气的中位时间分别为5天、7天和9天。该研究已于5月21日在线发表在《JAMA》上(doi: 10.1001/jama.2012.5669)。

加拿大多伦多大学重症医学系主任Niall D. Ferguson博士和多伦多大学医学教授兼桑尼布鲁克健康科学中心创伤/急重症项目负责人Gordon D. Rubenfeld博士报告称，新定义是根据国际专家小组的共识意见拟定的，并且通过来自7个中心2个大规模数据集共计4,457例患者的meta分析进行了经验验证。欧洲急危重症医学学会于2011年在德国柏林组建了一个专家小组来拟定ARDS新定义，希望在1994年美国-欧洲共识会议(AECC)所提出定义的基础上进一步完善。自AECC定义被广泛采纳以来，出现了一些关于信度和效度的问题。美国胸科学会和重症医学学会也对2011年的这次共识行动表示支持。

依照新的柏林定义，轻度ARDS患者存在轻度缺氧，定义为动脉血氧分压/吸入氧气分数比值介于201~300 mmHg (PaO₂/FIO₂= 201~300 mmHg)；中度缺氧者(PaO₂/FIO₂=101~200 mmHg)则为中度ARDS患者，重度缺氧者(PaO₂/FIO₂≤100 mmHg)为重度ARDS患者。

研究者报告称，柏林定义最初还纳入了重度ARDS的4项辅助参数，但后来开展的meta分析显示，这些参数并不能提高该定义对病死率的预测价值，于是将其删除。被去掉的参数分别为：影像学严重程度、呼吸系统顺应性、呼气末正压和经校正的每分钟呼气量。

Rubenfeld博士强调道，这些参数对于临床医生评估和理解ARDS仍然具有十分重要的意义，只是因为增加这些参数会使定义变得很复杂而且也不能提高定义的预测价值，所以才没有纳入重度ARDS的定义。他还提醒道：“柏林定义和AECC定义本身并不是一个预后模型；我们只是采用了病死率这一终点来完善柏林定义。”

逻辑回归模型分析显示，根据ROC曲线下面积(AUROC)的计算结果，柏林定义对病死率的预测效度高于AECC定义。柏林定义的AUROC为0.577，而AECC定义为0.536，差异有统计学意义。

研究者报告称，meta分析数据来自4项多中心临床研究和3项单中心生理学研究。22%的患者符合柏林定义的轻度ARDS诊断标准，50%符合中度ARDS，28%符合重度ARDS。病情越轻，无需使用呼吸机的中位时间就越短，轻度、中度和重度ARDS患者分别为20天、16天和1天。基线时依照柏林定义被归为轻度ARDS的患者中，7天内29%进展为中度ARDS，4%进展为重度ARDS。基线时被归为中度ARDS的患者中，7天内13%进展为重度ARDS。

研究者指出，这种将共识讨论与经验评价相结合的方法可能成为一种模式，便于将来制定出更加准确的基于证据的危重症定义。过去的ARDS定义只是单纯依靠专家共识。Rubenfeld博士说，正是因为开展了经验评价才删除了最初提出的几项辅助参数，否则我们提出的将是一个实际上没有必要的复杂的ARDS定义。

这项研究由欧洲危重症医学会、美国国立卫生研究院以及加拿大卫生研究院(CIHR)共同资助。CareFusion也友情资助了这项研究。Ferguson博士荣获了CIHR研究新人奖。Rubenfeld博士声明与Ikaria、Faron和Cerus公司存在经济利益关系。部分其他作者声明与Maquet Medical、Hemodec、Faron、阿斯利康、U.S. Biotest、Sirius Genetics、赛诺菲-安万特、Immunetrics、雅培、礼来、Ikaria、葛兰素史克、Tarix、Apeiron和(或)Novalung公司存在经济利益关系。

新定义有助于学术研究，也能提高临床医生对ARDS的认识

美国科罗拉多大学医学教授/危重症医学系主任Marc Moss博士在评价这一新定义时说：“过去AECC共识会议对ARDS的定义显然是有问题的。对于氧合标准、急性肺损伤与ARDS的鉴别、急性肺损伤的时间标准都存在一些不确定性。而且在胸腔摄片评分结果的判读上也存在一些变异性，旧版定义可能还排除了置入了肺动脉导管的患者的疑似肺水肿。” 他说：“这些研究者试图来解决其中一些问题。他们所采用的方法非常新颖，既独特又合理。对于通过符合某种标准来定义某种疾病的其他综合征，我认为也可以采用这种方法来制定定义。”

Moss博士指出：“新的定义将提高相关研究的可推广性，也更加便于开展急性肺损伤的临床试验，尤其是在发现对于最严重的ARDS患者唯一有用的潜在疗法方面。”“就临床实践而言，我现在还不能确定这是否会带来很大的变化，但应该会提高ARDS定义的统一性。此外，通过在影响力颇高的期刊上发表新版ARDS定义，这可能有助于提高临床医生对ARDS患者的认识。认识提高了，临床医生才会更加迅速地予以合理的治疗，比如只要患者血液动力学稳定，就可以采用低潮气量通气或限制性液体管理策略。

Moss博士声明无相关利益冲突。

ARDS柏林定义

• 时间：已知临床发病或呼吸症状新发或加重后1周内。

• 胸腔影像学改变：X线或CT扫描示双肺致密影，并且胸腔积液、肺叶/肺塌陷或结节不能完全解释。

• 肺水肿原因：无法用心力衰竭或体液超负荷完全解释的呼吸衰竭。如果不存在危险因素，则需要进行客观评估(例如超声心动图)以排除流体静力型水肿。

• 氧合状态：

轻度：PaO₂/FIO₂=201~300 mmHg，且呼气末正压(PEEP)或持续气道正压(CPAP)≤5 cm H₂O

中度：PaO₂/FIO₂=101~200 mmHg，且PEEP≥5 cm H₂O

重度：PaO₂/FIO₂≤100 mmHg，且PEEP≥10 cm H₂O

如果海拔高于1,000 m，校正因子应计算为PaO₂/FIO₂×(大气压力/760)。

爱思唯尔  版权所有


 

BY SHERRY BOSCHERT
Elsevier Global Medical News
Breaking News

SAN FRANCISCO (EGMN) – A proposed new definition of acute respiratory distress syndrome describes categories based on mild, moderate, or severe hypoxemia that correlate increasing severity with significantly increased mortality or increased time on mechanical ventilation among survivors.

The draft definition, created under consensus process by an international panel of experts, was refined by empirical testing in a meta-analysis of data on 4,457 patients in two large data sets from seven centers. The risk of mortality from acute respiratory distress syndrome (ARDS) was 27% with mild disease, 32% with moderate ARDS, and 45% with severe ARDS, Dr. Niall D. Ferguson and Dr. Gordon D. Rubenfeld reported at an international conference of the American Thoracic Society.

The median duration of mechanical ventilation in survivors was 5 days in patients with mild ARDS, 7 days with moderate ARDS, and 9 days with severe ARDS, said Dr. Ferguson, director of critical care medicine at the University of Toronto. The study was published online May 21 in JAMA (doi: 10.1001/jama.2012.5669).

The European Society of Intensive Care Medicine convened the panel of experts in Berlin in 2011 to draft a new definition of ARDS in hopes of improving upon the 1994 definition from the American-European Consensus Conference (AECC), said Dr. Rubenfeld, professor of medicine at the University of Toronto and chief of the program in trauma/emergency and critical care at Sunnybrook Health Sciences Center, Toronto. Since the AECC definition was adopted widely, issues of reliability and validity have emerged. The American Thoracic Society and the Society of Critical Care Medicine endorsed the 2011 consensus effort.

Under the new Berlin Definition, patients with mild ARDS have mild hypoxemia, defined as a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen of 201-300 mm Hg (PaO2/FIO2 = 201-300 mm Hg). Moderate hypoxia (PaO2/FIO2 = 101-200 mm Hg) defines moderate ARDS, and severe hypoxia (PaO2/FIO2 = 100 mm Hg or less) defines severe ARDS.

The initial draft of the Berlin Definition included four ancillary variables for severe ARDS that were dropped after the meta-analysis found that they did not improve the predictive value for mortality, the speakers and their associates in the study reported. The abandoned variables were radiographic severity, respiratory system compliance, positive end-expiratory pressure, and corrected expired volume per minute.

Dr. Rubenfeld stressed that these variables still are important for clinicians to measure and for understanding ARDS, but they were not included in the definition of severe ARDS because they made the definition more complex while not adding anything to the predictive value of the definition.

He also cautioned that neither the Berlin Definition nor the AECC definition is designed to be a prognostic model; the end point of mortality was used to hone the Berlin Definition.

The Berlin Definition had better predictive validity for mortality than the AECC definition in an analysis using the area under the receiver operating curve (AUROC) in logistic regression models. The Berlin Definition had an AUROC of 0.577, compared with 0.536 for the AECC definition, a statistically significant improvement.

The data for the meta-analysis came from four multicenter clinical studies and three single-center physiological studies, the investigators reported.

Twenty-two percent of patients met the Berlin Definition criteria for mild ARDS, 50% had moderate ARDS, and 28% had severe ARDS. Median ventilator-free days declined with severity of disease, from 20 days with mild ARDS to 16 days with moderate ARDS and 1 day with severe ARDS.

Among patients with mild ARDS at baseline under the Berlin Definition, 29% progressed to moderate disease and 4% progressed to severe disease within 7 days. Among patients with moderate ARDS at baseline, 13% progressed to severe disease within 7 days.

The investigators suggested that this approach of combining consensus discussions with empirical evaluation might be a model for creating more accurate, evidence-based definitions for critical illness syndromes. Previous ARDS definitions relied on expert consensus alone.

Without the empirical evaluation that led to deleting the ancillary variables, a needlessly complex ARDS definition would have been proposed, Dr. Rubenfeld said.

The study was sponsored by the European Society of Intensive Care Medicine, the U.S. National Institutes of Health, and the Canadian Institutes of Health Research (CIHR). CareFusion provided in-kind support for the study. Dr. Ferguson was supported by a CIHR New Investigator Award. Dr. Rubenfeld reported having financial relationships with Ikaria, Faron, and Cerus. Some of his associates in the study reported financial relationships with Maquet Medical, Hemodec, Faron, AstraZeneca, U.S. Biotest, Sirius Genetics, Sanofi-Aventis, Immunetrics, Abbott, Eli Lilly, Ikaria, GlaxoSmithKline, Tarix, Apeiron, and/or Novalung

Findings Good for Research, Awareness of ARDS

When asked to comment on the new definition, Dr. Marc Moss, professor of medicine and head of critical care at the University of Colorado, Denver, said, “There were apparent problems with the old AECC consensus conference definition of ARDS. There was some uncertainty about the oxygenation criteria, the differentiation between acute lung injury and ARDS, and the timing criteria for acute lung injury. There was some variability in the interpretation of the chest radiographic scores, and the old definition was said to exclude suspected pulmonary edema with a pulmonary artery catheter,” said Dr. Moss.

 “These investigators tried to address a few of those issues. The methodology that they used was very innovative, novel, unique, and sound. I think the methodology could be used in other syndromes where people are defined as having the disorder by meeting certain criteria,” he said.

“This study will improve the generalizability of the research and will make it easier to perform clinical trials for acute lung injury, especially by identifying potential therapies that maybe are only useful for those patients who have the most severe form of ARDS,” Dr. Moss noted.

 “In terms of pure clinical practice, I’m not sure that it will make a large change, but it might lead to some uniformity of the definition of ARDS. Also, by publishing a new definition of ARDS in a high-impact journal, this might raise awareness of patients who have ARDS. With increased awareness, clinicians would more readily implement therapies that should be used, such as low tidal volume ventilation or a fluid-conservative strategy once the patient is hemodynamically stable,” he said.

Dr. Moss reported having no relevant disclosures.

The Berlin Definition of ARDS

•Timing: Within 1 week of a known clinical insult or new or worsening respiratory symptoms.

•Chest imaging: Bilateral opacities on x-ray or CT scan not fully explained by effusions, lobar/lung collapse, or nodules.

•Origin of edema: Respiratory failure not fully explained by cardiac failure or fluid overload. Need objective assessment (for example, echocardiography) to exclude hydrostatic edema if no risk factor present.

•Oxygenation:

Mild: PaO2/FIO2 of 201-300 mm Hg with positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) of 5 cm H2O or greater.

Moderate: PaO2/FIO2 of 101-200 mm Hg with PEEP of 5 cm H2O or greater.

Severe: PaO2/FIO2 of 100 mm Hg or less with PEEP of 5 cm H2O or greater.

If the altitude is higher than 1,000 m, the correction factor should be calculated as PaO2/RO2 × (barometric pressure/760).