Pulmonary Section, Veterans Affairs Medical Center, Washington, DC, USA.
Crit Care Med. 2012 Feb;40(2):495-501. doi: 10.1097/CCM.0b013e318232da5e.
Evaluate the effects of methylprednisolone on markers of inflammation, coagulation, and angiogenesis during early acute respiratory distress syndrome.
Retrospective analysis.
Four intensive care units.
Seventy-nine of 91 patients with available samples enrolled in a randomized, blinded controlled trial.
Early methylprednisolone infusion (n = 55) compared with placebo (n = 24).
Interleukin-6, tumor necrosis factor α, vascular endothelial growth factor, protein C, procalcitonin, and proadrenomedullin were measured in archived plasma. Changes from baseline to day 3 and day 7 were compared between groups and in subgroups based on the precipitating cause of acute respiratory distress syndrome. Methylprednisolone therapy was associated with greater improvement in Lung Injury Score (p = .003), shorter duration of mechanical ventilation (p = .005), and lower intensive care unit mortality (p = .05) than control subjects. On days 3 and 7, methylprednisolone decreased interleukin-6 and increased protein C levels (all p < .0001) compared with control subjects. Proadrenomedullin levels were lower by day 3 with methylprednisolone treatment (p = .004). Methylprednisolone decreased interleukin-6 by days 3 and 7 in patients with pulmonary causes of acute respiratory distress syndrome but only at day 3 in those with extrapulmonary causes of acute respiratory distress syndrome. Protein C levels were increased with methylprednisolone on days 3 and 7 in patients with infectious and/or pulmonary causes of acute respiratory distress syndrome (all p < .0001) but not in patients with noninfectious or extrapulmonary causes of acute respiratory distress syndrome. Proadrenomedullin levels were decreased with methylprednisolone on day 3 in patients with infectious or extrapulmonary causes of acute respiratory distress syndrome (both p ≤ .008) but not in noninfectious or pulmonary acute respiratory distress syndrome. Tumor necrosis factor, vascular endothelial growth factor, and procalcitonin were elevated but not differentially affected by methylprednisolone therapy.
In early acute respiratory distress syndrome, administration of methylprednisolone was associated with improvement in important biomarkers of inflammation and coagulation and clinical outcomes. Biomarker changes varied with the precipitating cause of acute respiratory distress syndrome, suggesting that the underlying mechanisms and response to anti-inflammatory therapy may vary with the cause of acute respiratory distress syndrome.
评估甲泼尼龙对早期急性呼吸窘迫综合征炎症、凝血和血管生成标志物的影响。
回顾性分析。
4 个重症监护病房。
91 例患者中，79 例有可用样本，纳入一项随机、双盲对照试验。
早期甲泼尼龙输注（n=55）与安慰剂（n=24）比较。
检测存档血浆中的白细胞介素-6、肿瘤坏死因子-α、血管内皮生长因子、蛋白 C、降钙素原和前肾上腺髓质素。比较两组间和根据急性呼吸窘迫综合征诱发原因的亚组间从基线到第 3 天和第 7 天的变化。与对照组相比，甲泼尼龙治疗组急性呼吸窘迫综合征的肺损伤评分（p=0.003）改善更大，机械通气时间更短（p=0.005），重症监护病房死亡率更低（p=0.05）。第 3 天和第 7 天，与对照组相比，甲泼尼龙降低白细胞介素-6并升高蛋白 C 水平（均 p<0.0001）。甲泼尼龙治疗第 3 天前肾上腺髓质素水平降低（p=0.004）。甲泼尼龙治疗急性呼吸窘迫综合征肺源性患者第 3 天和第 7 天白细胞介素-6降低，但仅在第 3 天肺外源性患者降低。蛋白 C 水平在感染和/或肺源性急性呼吸窘迫综合征患者中，甲泼尼龙在第 3 天和第 7 天升高（均 p<0.0001），而非感染性或肺外源性急性呼吸窘迫综合征患者则没有升高。感染或肺外源性急性呼吸窘迫综合征患者甲泼尼龙治疗第 3 天前肾上腺髓质素水平降低（均 p≤0.008），而非感染性或肺源性急性呼吸窘迫综合征患者则没有。肿瘤坏死因子、血管内皮生长因子和降钙素原升高，但不受甲泼尼龙治疗的影响。
在早期急性呼吸窘迫综合征中，给予甲泼尼龙可改善炎症和凝血的重要生物标志物，并改善临床结局。生物标志物的变化与急性呼吸窘迫综合征的诱发原因有关，这表明急性呼吸窘迫综合征的潜在机制和对抗炎治疗的反应可能因病因而异。
