Peritoneal Membrane Oxygenation Therapy for Rats With Acute Respiratory Distress Syndrome 1
Peritoneal Membrane Oxygenation Therapy for Rats With Acute Respiratory Distress Syndrome 1
复制标题
急性呼吸窘迫综合征大鼠腹膜氧合疗法1
DOI：
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
B. Terry
中科院分区：
文献类型：
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作者：
Nathan D. Legband;Liana Hatoum;A. Thomas;Craig Kreikemeier;D. Hostetler;K. Buesing;M. Borden;B. Terry
在接受重症监护的患者中，56%患有或将获得急性呼吸衰竭（ARF），其中略少于三分之一的患者进展为最严重的呼吸衰竭形式，称为急性呼吸窘迫综合征（ARDS）[1]。有效的氧气输送方法对于改善ARF和ARDS的结局至关重要;然而，根据目前可用的医学治疗，这些病例的死亡率报告为32-75% [1]。因此，研究继续寻找更有效和高效的氧气输送方式，以允许ARDS中受损肺实质的愈合时间。人们已经探索了绕过并减轻受损肺部压力的充氧方法，以促进肺部休息和恢复。迄今为止，只有体外膜氧合（ECMO）已被批准用于医疗用途。然而，ECMO固有的几个风险-包括出血，血栓形成和插管故障-否定了它对几个患者人群的潜在益处，包括那些有出血风险或持续创伤性脑损伤的患者。此外，ECMO需要庞大的设备，广泛的技术培训，并且价格昂贵-所有这些都限制了它在重症监护病房环境之外的使用。这些限制和风险使ECMO成为许多人可行的治疗替代方案，使临床医生几乎无法为患者及其家属提供帮助。我们开发了一种新的医疗器械，通过将磷脂壳氧微泡（OMB）输送到腹膜腔来提供补充氧合。之前，我们已经证明腹膜氧合（PMO）是在缺氧和急性肺损伤模型期间输送氧气的治疗方法[2]。我们现在正在探索PMO治疗具有更大临床相关性的疾病模型，如ARDS。文献中已经充分建立了ARDS的鼠模型，并且通常通过内毒素、脂多糖（LPS）的气管内递送来创建[3]。在这项研究中，我们诱导大鼠的ARDS，提供OMB或对照溶液的腹膜腔与流动输液装置，并评估PMO治疗作为一种治疗相比，对照溶液。我们认为PMO治疗有可能成为严重呼吸衰竭患者的安全可靠的肺转流治疗，这些患者不能耐受ECMO固有的重大风险。随着我们向临床转化的进展，我们预计PMO将应用于重症监护病房、军事战斗环境和太空探索飞行器。
Of patients admitted to intensive care, 56% possess or will acquire acute respiratory failure (ARF) with slightly less than onethird of these patients progress to the most severe form of respiratory failure known as acute respiratory distress syndrome (ARDS) [1]. Effective methods of oxygen delivery are essential to improve outcomes in ARF and ARDS; however, with currently available medical treatments the mortality rate in these cases has been reported at 32–75% [1]. Therefore, research continues to look for more effective and efficient modalities of oxygen delivery to allow time for healing of the impaired lung parenchyma seen in ARDS. Methods of oxygenation which bypass and reduce the strain on damaged lungs have been explored in an effort to promote lung rest and recovery. To date, only extracorporeal membrane oxygenation (ECMO) has been approved for medical use. However, inherent to ECMO are several risks—including hemorrhage, thrombosis, and cannula malfunction—which negate its potential benefits for several patient populations, including those at risk for bleeding or who have sustained traumatic brain injury. In addition, ECMO requires bulky equipment, extensive technical training, and is expensive—all of which limit its use outside of the intensive care unit setting. These limitations and risks eliminate ECMO as a viable treatment alternative for many, leaving clinicians with little to offer patients and their families. We have developed a new medical device to provide supplemental oxygenation by delivering phospholipid shelled oxygen microbubbles (OMBs) to the peritoneal cavity. Previously, we have shown that peritoneal membrane oxygenation (PMO) is a treatment method for delivering oxygen during hypoxia and acute lung injury models [2]. We are now exploring PMO therapy for disease models that have greater clinical relevance, such as ARDS. Murine models of ARDS have been well established in the literature and are typically created by intratracheal delivery of the endotoxin, lipopolysaccharide (LPS) [3]. In this study, we induce ARDS in rats, deliver OMB or control solutions to the peritoneal cavity with an ambulatory infusion device, and evaluate PMO therapy as a treatment compared to control solutions. We believe that PMO treatment has the potential to be a safe and reliable lung bypass therapy for patients with severe respiratory failure who cannot tolerate the significant risk profile inherent to ECMO. As we progress to clinical translation, we expect application of PMO in intensive care units, military combat settings, and space exploration vehicles.