澳大利亚奥斯汀医院Rinaldo Bellomo团队的研究比较了维生素C+氢化可的松+硫胺素与单纯氢化可的松对脓毒性休克患者存活和无血管加压素时间的影响。该研究于2020年1月17日发表于国际一流学术期刊《美国医学会杂志》上。

维生素C+氢化可的松+硫胺素与单独氢化可的松相比，是否能更有效地治疗脓毒性休克尚未清楚。

2018年5月8日至2019年10月6日，研究组在澳大利亚、新西兰和巴西的10个重症监护病房了进行了一项多中心、开放标签、随机临床试验，共招募了216名脓毒症休克患者。将其随机分组，其中109名接受静脉注射维生素C+氢化可的松+硫胺素（干预组），107名接受静脉注射氢化可的松（对照组），直至休克缓解，两组用药均不超过10天。

共有211例患者纳入最终分析，平均年龄为61.7岁。干预组到第7天的存活和无加压素时间为122.1小时，对照组为124.6小时，差异无统计学意义。干预组的90天死亡率为28.6%，对照组为24.5%，风险比为1.18。其他临床指标两组间均无显著差异，且均无严重不良事件发生。

总之，与单独静脉注射氢化可的松相比，静脉注射维生素C+氢化可的松+硫胺素治疗脓毒性休克的患者，7天存活和不使用加压素的时间均未得到显著改善。

附：英文原文

Title: Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock: The VITAMINS Randomized Clinical Trial

Author: Tomoko Fujii, Nora Luethi, Paul J. Young, Daniel R. Frei, Glenn M. Eastwood, Craig J. French, Adam M. Deane, Yahya Shehabi, Ludhmila A. Hajjar, Gisele Oliveira, Andrew A. Udy, Neil Orford, Samantha J. Edney, Anna L. Hunt, Harriet L. Judd, Laurent Bitker, Luca Cioccari, Thummaporn Naorungroj, Fumitaka Yanase, Samantha Bates, Forbes McGain, Elizabeth P. Hudson, Wisam Al-Bassam, Dhiraj Bhatia Dwivedi, Chloe Peppin, Phoebe McCracken, Judit Orosz, Michael Bailey, Rinaldo Bellomo

Issue&Volume: January 17, 2020

Abstract:

Importance  It is unclear whether vitamin C, hydrocortisone, and thiamine are more effective than hydrocortisone alone in expediting resolution of septic shock.

Objective  To determine whether the combination of vitamin C, hydrocortisone, and thiamine, compared with hydrocortisone alone, improves the duration of time alive and free of vasopressor administration in patients with septic shock.

Design, Setting, and Participants  Multicenter, open-label, randomized clinical trial conducted in 10 intensive care units in Australia, New Zealand, and Brazil that recruited 216 patients fulfilling the Sepsis-3 definition of septic shock. The first patient was enrolled on May 8, 2018, and the last on July 9, 2019. The final date of follow-up was October 6, 2019.

Interventions  Patients were randomized to the intervention group (n=109), consisting of intravenous vitamin C (1.5 g every 6 hours), hydrocortisone (50 mg every 6 hours), and thiamine (200 mg every 12 hours), or to the control group (n=107), consisting of intravenous hydrocortisone (50 mg every 6 hours) alone until shock resolution or up to 10 days.

Main Outcomes and Measures  The primary trial outcome was duration of time alive and free of vasopressor administration up to day 7. Ten secondary outcomes were prespecified, including 90-day mortality.

Results  Among 216 patients who were randomized, 211 provided consent and completed the primary outcome measurement (mean age, 61.7 years [SD, 15.0]; 133 men [63%]). Time alive and vasopressor free up to day 7 was 122.1 hours (interquartile range [IQR], 76.3-145.4 hours) in the intervention group and 124.6 hours (IQR, 82.1-147.0 hours) in the control group; the median of all paired differences was –0.6 hours (95% CI, –8.3 to 7.2 hours; P=.83). Of 10 prespecified secondary outcomes, 9 showed no statistically significant difference. Ninety-day mortality was 30/105 (28.6%) in the intervention group and 25/102 (24.5%) in the control group (hazard ratio, 1.18; 95% CI, 0.69-2.00). No serious adverse events were reported.

Conclusions and Relevance  In patients with septic shock, treatment with intravenous vitamin C, hydrocortisone, and thiamine, compared with intravenous hydrocortisone alone, did not significantly improve the duration of time alive and free of vasopressor administration over 7 days. The finding suggests that treatment with intravenous vitamin C, hydrocortisone, and thiamine does not lead to a more rapid resolution of septic shock compared with intravenous hydrocortisone alone.

DOI: 10.1001/jama.2019.22176

Source: https://jamanetwork.com/journals/jama/fullarticle/2759414