117316Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, USA.
309953David Geffen School of Medicine at UCLA, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
J Intensive Care Med. 2022 May;37(5):693-697. doi: 10.1177/08850666211038883. Epub 2021 Sep 13.
To test the benefits of Solumedrol treatment in sepsis patients with a blunted adrenocorticotropic hormone (ACTH)-cortisol response (delta <13 µg/dL) with regard to the number of days on ventilator, days on intravenous blood pressure support, length of time in an intensive care unit (ICU), 14-day mortality, and 28-day mortality. The trial was prospective, randomized, and double-blind. As part of a larger sepsis trial, 54 patients with sepsis had an intravenous ACTH stimulation test using 250 µg of ACTH, and serum cortisol was measured at times 0, 30, and 60 min. Eleven patients failed to increase their cortisol concentration above 19.9 µg/dL and were excluded from the clinical trial as they were considered to have adrenal insufficiency. The remaining 43 patients had a baseline cortisol of 32 ± 1 µg/dL increased to 38 ± 3 µg/dL at 30 min and 40 ± 3 at 60 min. All cortisol responses were <12.9 µg/dL between time 0 and time 60, which is defined as a blunted cortisol response to intravenous ACTH administration. Twenty-one were randomized to receive 20 mg of intravenous Solumedrol and 22 were randomized to receive a matching placebo every 8 h for 7-days. There was no significant difference between the two randomized groups. Data analysis was carried out bya two-tailed test and < .05 as significant.
The mean age was 51 ± 2 (mean ± SEM) with 61% female. Groups were well matched with regard to APACHE III score in Solumedrol versus placebo (59 ± 6 vs 59 ± 6), white blood cell count (18.8 ± 2.2 vs 18.6 ± 2.6), and incidence of bacteremia (29 vs 39%). The 28-day mortality rate was reduced in the Solumedrol treated arm (43 ± 11 vs 73 ± 10%; < .05). There was no change in days in ICU, days on blood pressure agents, or days on ventilator. Seven days of high-dose intravenous Solumedrol treatment (20 mg every 8 h) in patients with a blunted cortisol response to ACTH was associated with an improved 28-day survival. This small study suggests that an inability to increase endogenous cortisol production in patients with sepsis who are then provided steroid treatment could improve survival.
测试在促肾上腺皮质激素（ACTH）-皮质醇反应减弱（delta <13μg/dL）的脓毒症患者中，使用 Solumedrol 治疗的益处，具体表现在呼吸机使用天数、静脉内血压支持天数、重症监护病房（ICU）时间、14 天死亡率和 28 天死亡率。该试验为前瞻性、随机、双盲。作为一项较大的脓毒症试验的一部分，54 例脓毒症患者接受了 250μg ACTH 的静脉内 ACTH 刺激试验，并在 0、30 和 60 分钟时测量血清皮质醇。11 例患者未能将皮质醇浓度升高至 19.9μg/dL 以上，因此被排除在临床试验之外，因为他们被认为患有肾上腺功能不全。其余 43 例患者的基础皮质醇为 32±1μg/dL，30 分钟时升高至 38±3μg/dL，60 分钟时升高至 40±3μg/dL。所有皮质醇反应均在 0 至 60 分钟之间<12.9μg/dL，这被定义为对静脉内 ACTH 给药的皮质醇反应减弱。21 例患者随机接受 20mg 静脉注射甲泼尼龙，22 例患者随机接受匹配的安慰剂，每 8 小时 1 次，共 7 天。两组间无显著差异。数据分析采用双尾检验，p<0.05 为有统计学意义。
平均年龄为 51±2（平均值±SEM），女性占 61%。两组的急性生理学和慢性健康状况评分系统 III（APACHE III）评分在甲泼尼龙组和安慰剂组中匹配良好（59±6 vs 59±6），白细胞计数（18.8±2.2 vs 18.6±2.6）和菌血症发生率（29%vs 39%）。在接受甲泼尼龙治疗的患者中，28 天死亡率降低（43±11 vs 73±10%；p<0.05）。ICU 天数、血压药物使用天数或呼吸机使用天数均无变化。对 ACTH 皮质醇反应减弱的脓毒症患者给予 7 天高剂量静脉内甲泼尼龙治疗（每 8 小时 20mg）可提高 28 天生存率。这项小型研究表明，对接受类固醇治疗的脓毒症患者不能增加内源性皮质醇生成，可能会提高生存率。
