Reassessing recombinant human activated protein C for sepsis: time for a new randomized controlled trial.
Reassessing recombinant human activated protein C for sepsis: time for a new randomized controlled trial.
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重新评估重组人活化蛋白 C 治疗脓毒症：是时候进行新的随机对照试验了。
DOI：
10.1097/01.ccm.0000183002.26587.ff
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发表时间：
2005
影响因子：
8.8
通讯作者：
Natanson,Charles
中科院分区：
文献类型：
--
作者：
Eichacker,PeterQ;Danner,RobertL;Suffredini,AnthonyF;Cui,Xizhong;Natanson,Charles
它与30%的死亡率相关（1），出院后幸存者的生活质量下降（2）。我们仍然缺乏有效的治疗，可能部分原因是我们目前的ARDS定义导致临床试验中招募的患者在肺损伤的严重程度、病因（例如，原发性与继发性）和/或表现方式（例如，弥漫性与局限性ARDS）方面存在差异（3）。对于一个明确定义的实体（如肺炎），比目前归类在ARDS“保护伞”下的松散相关实体更容易找到有效的治疗方法。目前对ARDS患者的治疗主要包括正压呼吸支持。虽然机械通气的主要目的是广泛同意的恢复/维持足够的气体交换和实施肺保护策略，以争取时间肺修复的最佳方式来实现这一点是有争议的，特别是在困难的患者。例如，在存在顽固性低氧血症的情况下，已经提出了不同的抢救策略，包括吸入血管扩张剂（一氧化氮或前列环素）、高水平的呼气末正压（PEEP）、复张操作、俯卧位（PP）、高频振荡通气（HFOV）或体外膜氧合。这些策略都没有被证明可以改善结果，并且对这些技术的最初热情几乎总是伴随着失望。实验工作已经确定（4）a）正压通气可以诱导内皮和上皮功能障碍和结构损伤; B）潮气量的大小相对于必须容纳后者的肺的大小是肺泡过度扩张和损伤的关键决定因素（体积创伤）（5）;和c）需要足够水平的PEEP以保护肺免受周期性气道开放和塌陷（肺不张）和/或还免受与大潮气偏移相关的应变和应力（5，6）。然而，我们仍在争论如何最好地保护肺部免受呼吸机诱导的肺损伤（VILI）。尽管临床上已经证实需要避免潮气量过大（7），但最近的一项大型多中心研究未能证实PEEP的保护作用（8）。正如最近指出的那样，这可能是招募不同形式肺损伤患者和本研究中使用的特定PEEP滴定方案的可变反应的综合结果（9）。PP和HFOV已被提议作为传统机械通气和PEEP的替代策略，特别是在表现不佳的患者中，因为它们具有改善气体交换和预防VILI发展的双重潜力。总体而言，70%的急性肺损伤/ARDS患者在俯卧时PaO 2/FIO 2比值改善（10）。此外，在ARDS的局部形式中，PP似乎比PEEP特别有利（11）。HFVO改善选定成人难治性ARDS患者血气的能力已在非对照系列中报道（12）。然而，在最近的一项随机试验中，观察到死亡率没有显著差异，气体交换只有短暂的改善（13）。如俯卧试验（10，14）中所报告的，改善的气体交换不一定转化为更好的结果。事实上，正如从ARDSnet试验（7）中了解到的那样，给定的缓解策略如何调节肺应激和损伤是一个更重要的决定因素
It is associated with a mortality rate of 30%(1), and the quality of life of survivors is reduced after discharge (2). We are still lacking effective treatment, possibly in part because our current ARDS definition leads to the enrollment of patients in clinical trials who differ with respect to severity, etiology (eg, primary vs. secondary), and/or mode of presentation (eg, diffuse vs. localized ARDS) of lung injury (3). It is likely easier to find an effective treatment for a well-defined entity (eg, pneumonia) than for the number of loosely related entities currently grouped under the ARDS “umbrella.” The treatment of patients with ARDS currently consists essentially of ventilatory support with positive pressure. Although the key objectives of mechanical ventilation are widely agreed on—restoration/maintenance of adequate gas exchange and implementation of a lung-protective strategy to buy time for lung repair—the best way to achieve this is controversial, particularly in difficult patients. In the presence of refractory hypoxemia, for instance, different rescue strategies have been proposed including inhaled vasodilator (nitric oxide or prostacyclin), a high level of positive end-expiratory pressure (PEEP), recruitment maneuvers, prone positioning (PP), high-frequency oscillatory ventilation (HFOV), or extracorporeal membrane oxygenation. None of these strategies has been proven to improve outcome, and the initial enthusiasm for these techniques has almost invariably been followed by disappointment.Experimental works have established (4) that a) positive pressure ventilation can induce endothelial and epithelial dysfunctional and structural injury; b) the magnitude of the tidal volume relative to the size of the lung that must accommodate the latter is a key determinant of alveolar overdistension and injury (volutrauma)(5); and c) an adequate level of PEEP is needed to protect the lungs from cyclic airway opening and collapse (atelectrauma) and/or also from the strain and stress associated with large tidal excursion (5, 6). We are, however, still debating how to best protect the lungs from ventilator-induced lung injury (VILI). Although the need to avoid excessive tidal volume is now clinically confirmed (7), a recent large multiple-center study failed to confirm the protective effect of PEEP (8). This may have been the combined consequence of enrollment of patients with different forms of lung injury and variable responses to the specific PEEP titration protocol used in this study, as recently pointed out (9). PP and HFOV have been proposed as alternative strategies to conventional mechanical ventilation and PEEP, particularly in patients doing poorly, given their dual potential to improve gas exchange and prevent the development of VILI. Overall, 70% of patients with acute lung injury/ARDS experience improved PaO2/FIO2 ratio when turned prone (10). In addition, PP appears to be particularly advantageous over PEEP in the localized forms of ARDS (11). HFVO’s ability to improve blood gas in selected adults with difficult to treat ARDS has been reported in uncontrolled series (12). In a recent randomized trial, however, no significant difference in mortality rate and only a transient improvement in gas exchange were observed (13). As reported in the prone trials (10, 14), improved gas exchange does not necessarily translate into better outcome. Indeed, as learned from the ARDSnet trial (7), how a given ventilatory strategy modulates lung stress and injury is a more important determinant
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影响因子：
3.3
作者：
LEMEN, R;BENSON, M;JONES, JG
通讯作者：
JONES, JG
影响因子：
7.3
作者：
FLOWER, RJ;HARVEY, EA;KINGSTON, WP
通讯作者：
KINGSTON, WP
豚鼠的两个品系对化学介质和过敏反应敏感和不敏感。
DOI：
--
发表时间：
1971
期刊：
Journal of Allergy
影响因子：
--
作者：
Y. Takino;K. Sugahara;I. Horino
通讯作者：
I. Horino
大鼠近交系的衍生，在雾化抗原攻击后出现哮喘样症状。
影响因子：
6.4
作者：
G. Holme;H. Piechuta
通讯作者：
H. Piechuta
臭氧引起狗气道高反应性的时间过程。
DOI：
10.1152/jappl.1983.55.4.1232
发表时间：
1983
期刊：
Journal of applied physiology: respiratory, environmental and exercise physiology
影响因子：
--
作者：
Holtzman,MJ;Fabbri,LM;Skoogh,BE;O'Byrne,PM;Walters,EH;Aizawa,H;Nadel,JA
通讯作者：
Nadel,JA