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不同剂量甲泼尼龙治疗急性呼吸窘迫综合征的效果:来自动物和临床研究的结果。

Effects of different doses of methylprednisolone therapy on acute respiratory distress syndrome: results from animal and clinical studies.

机构信息

Department of Intensive Care Unit, Shengli Oilfield Central Hospital, Dongying, China.

Department of Obstetrics and Gynecology, Dongying Fifth People's Hospital, Dongying, China.

出版信息

BMC Pulm Med. 2022 Sep 16;22(1):348. doi: 10.1186/s12890-022-02148-y.

Abstract

BACKGROUND

The optimal dose of glucocorticoids for acute respiratory distress syndrome (ARDS) is uncertain. This study aimed to evaluate the effects of different doses of methylprednisolone on sepsis-induced acute lung injury (ALI) rats and a cohort of moderate and severe ARDS patients.

METHODS

ALI rats, challenged with lipopolysaccharide, were randomly received intraperitoneal injection of normal saline (model group) and different doses of methylprednisolone (0.5, 2, 8 mg/kg, named as low-, moderate- and high-dose group, respectively) for 5 days. The body weight changes of rats, inflammatory factors in bronchoalveolar lavage fluid (BALF), lung wet/dry ratio, histopathological score, and the mRNA expressions of glucocorticoid receptor α (GRα), GRβ and nuclear factor-κB (NF-κB) were measured. Forty moderate and severe ARDS patients were treated with standard of care or plus different doses of methylprednisolone (40, 80, 120 mg/day, named as low-, moderate- and high-dose group, respectively) for 5 days. Clinical outcomes were PaO/FiO ratio and C-reactive protein (CRP) level at day 5, intubation rate, hospital stay, 28-day mortality, and adverse events rate.

RESULTS

In animal experiment, different doses of methylprednisolone could increase the body weight of rats, and reduce inflammatory factors in BALF and the degree of lung injury compared with model group. The efficacy of methylprednisolone at moderate-dose was better than that at low-dose, but was equivalent to that at high-dose, which was consistent with the differential changes in the mRNA expression of GRα, GRβ and NF-κB. In clinical study, the moderate-dose group was associated with higher PaO/FiO ratio and lower CRP level. No significant difference in other clinical outcomes among groups was detected.

CONCLUSIONS

This study showed that the efficacy of methylprednisolone in ARDS treatment was not always dose-dependent due to the differential regulation of related receptors. The moderate-dose of methylprednisolone may be the potential optimal dose for ARDS treatment, which needs to be further verified by larger clinical trials.

摘要

背景

糖皮质激素治疗急性呼吸窘迫综合征(ARDS)的最佳剂量尚不确定。本研究旨在评估不同剂量甲泼尼龙对脂多糖诱导的急性肺损伤(ALI)大鼠和中度及重度 ARDS 患者的影响。

方法

采用脂多糖诱导的 ALI 大鼠模型,随机腹腔注射生理盐水(模型组)及不同剂量甲泼尼龙(0.5、2、8mg/kg,分别命名为低、中、高剂量组),连续 5 天。测量大鼠体重变化、支气管肺泡灌洗液(BALF)中炎症因子、肺湿/干重比、组织病理学评分以及糖皮质激素受体α(GRα)、GRβ 和核因子-κB(NF-κB)的 mRNA 表达。40 例中度及重度 ARDS 患者接受标准治疗或加用不同剂量甲泼尼龙(40、80、120mg/d,分别命名为低、中、高剂量组),连续 5 天。观察第 5 天的 PaO/FiO 比值和 C 反应蛋白(CRP)水平、气管插管率、住院时间、28 天死亡率和不良反应发生率。

结果

在动物实验中,与模型组相比,不同剂量的甲泼尼龙可增加大鼠体重,降低 BALF 中的炎症因子和肺损伤程度。中剂量甲泼尼龙的疗效优于低剂量组,但与高剂量组相当,这与 GRα、GRβ 和 NF-κB 的 mRNA 表达差异变化一致。在临床研究中,中剂量组的 PaO/FiO 比值较高,CRP 水平较低。各组间其他临床结局无显著差异。

结论

本研究表明,由于相关受体的差异调节,甲泼尼龙治疗 ARDS 的疗效并不总是呈剂量依赖性。中剂量甲泼尼龙可能是 ARDS 治疗的潜在最佳剂量,还需要更大规模的临床试验进一步验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4092/9482269/ab871c23dba9/12890_2022_2148_Fig1_HTML.jpg

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