PDF(Pubmed)
Abstract：
Whilst the presence of 2 subphenotypes among the heterogenous Acute Respiratory Distress Syndrome (ARDS) population is becoming clinically accepted, subphenotype-specific treatment efficacy has yet to be prospectively tested. We investigated anti-inflammatory treatment in different ARDS models in sheep, previously shown similarities to human ARDS subphenotypes, in a preclinical, randomized, blinded study. Thirty anesthetized sheep were studied up to 48 h and randomized into: (a) OA: oleic acid (n = 15) and (b) OA-LPS: oleic acid and subsequent lipopolysaccharide (n = 15) to achieve a PaO2/FiO2 ratio of < 150 mmHg. Then, animals were randomly allocated to receive treatment with methylprednisolone or erythromycin or none. Assessed outcomes were oxygenation, pulmonary mechanics, hemodynamics and survival. All animals reached ARDS. Treatment with methylprednisolone, but not erythromycin, provided the highest therapeutic benefit in Ph2 animals, leading to a significant increase in PaO2/FiO2 ratio by reducing pulmonary edema, dead space ventilation and shunt fraction. Animals treated with methylprednisolone displayed a higher survival up to 48 h than all others. In animals treated with erythromycin, there was no treatment benefit regarding assessed physiological parameters and survival in both phenotypes. Treatment with methylprednisolone improves oxygenation and survival, more so in ovine phenotype 2 which resembles the human hyperinflammatory subphenotype.
摘要：
虽然异质性急性呼吸窘迫综合征（ARDS）人群中存在2种亚表型，但临床上已被接受，亚表型特异性治疗疗效尚待前瞻性检验.我们研究了在绵羊不同ARDS模型中的抗炎治疗，先前显示与人类ARDS亚型相似，在临床前，随机化，盲目的研究。对30只麻醉的绵羊进行了长达48小时的研究，并随机分为：（a）OA：油酸（n=15）和（b）OA-LPS：油酸和随后的脂多糖（n=15），以达到PaO2/FiO2比率<150mmHg。然后，动物被随机分配接受甲基强的松龙或红霉素治疗或不接受治疗.评估结果是氧合，肺力学,血液动力学和存活率。所有动物都达到了ARDS。用甲基强的松龙治疗，但不是红霉素,在Ph2动物中提供最高的治疗益处，通过减少肺水肿导致PaO2/FiO2比率显着增加，死腔通风和分流部分。用甲基强的松龙治疗的动物显示出比所有其他动物更高的存活时间，直到48小时。在用红霉素治疗的动物中，在两种表型的评估生理参数和生存率方面,均无治疗获益.甲基强的松龙治疗可改善氧合和生存率，在类似于人类高炎性亚表型的绵羊表型2中更是如此。
