Data_Sheet_2_Impact of intravenous vitamin C as a monotherapy on mortality risk in critically ill patients: A meta-analysis of randomized controlled trials with trial sequential analysis.docx

BackgroundThis meta-analysis aimed at investigating the pooled evidence regarding the effects of intravenous vitamin C (IVVC) on mortality rate in critically ill patients.
MethodsDatabases including Medline, Embase, and Cochrane Library were searched from inception to October, 2022 to identify RCTs. The primary outcome was the risk of overall mortality. Subgroup analyses were performed based on IVVC dosage (i.e., cut-off value: 100 mg/kg/day or 10000 mg/day). Trial sequential analysis (TSA) was used to examine the robustness of evidence.
ResultsA total of 12 trials including 1,712 patients were analyzed. Although meta-analysis demonstrated a lower risk of mortality in patients with IVVC treatment compared to those without [risk ratio (RR): 0.76, 95% CI: 0.6 to 0.97, p = 0.02, I2 = 36%, 1,711 patients), TSA suggested the need for more studies for verification. Moreover, subgroup analyses revealed a reduced mortality risk associated with a low IVVC dosage (RR = 0.72, p = 0.03, 546 patients), while no beneficial effect was noted with high IVVC dosage (RR = 0.74, p = 0.13, I2 = 60%, 1,165 patients). The durations of vasopressor [mean difference (MD): −37.75 h, 404 patients) and mechanical ventilation (MD: −47.29 h, 388 patients) use were shorter in the IVVC group than those in the controls, while there was no significant difference in other prognostic outcomes (e.g., length of stay in intensive care unit/hospital) between the two groups.
ConclusionAlthough intravenous vitamin C as a monotherapy reduced pooled mortality, durations of vasopressor use and mechanical ventilation, further research is required to support our findings and to identify the optimal dosage of vitamin C in the critical care setting.
Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022371090.

背景：本项荟萃分析旨在整合现有汇总证据，探讨静脉注射维生素C（intravenous vitamin C, IVVC）对重症患者死亡率的影响。
方法：检索Medline、Embase及Cochrane Library数据库，检索时限设为从建库至2022年10月，以筛选随机对照试验（randomized controlled trial, RCT）。本研究的主要结局指标为全因死亡风险。依据IVVC给药剂量（截断值：100 mg/kg/天或10000 mg/天）开展亚组分析，并采用试验序贯分析（trial sequential analysis, TSA）检验证据的稳健性。
结果：共纳入12项试验，涉及1712例患者进行分析。尽管荟萃分析结果显示，与对照组相比，IVVC治疗组患者的死亡风险更低〔风险比（risk ratio, RR）=0.76，95%置信区间（95% CI）：0.6~0.97，P=0.02，I²=36%，纳入1711例患者〕，但试验序贯分析提示仍需开展更多研究以验证该结论。此外，亚组分析显示，低剂量IVVC给药可降低死亡风险（RR=0.72，P=0.03，纳入546例患者），而高剂量IVVC给药未观察到显著获益（RR=0.74，P=0.13，I²=60%，纳入1165例患者）。与对照组相比，IVVC组患者的血管活性药物使用时长〔均数差（mean difference, MD）=-37.75 h，纳入404例患者〕及有创机械通气时长（MD=-47.29 h，纳入388例患者）均更短，但两组在其他预后指标（如重症监护病房（intensive care unit, ICU）/住院时长）上无显著差异。
结论：尽管静脉注射维生素C单药治疗可降低汇总死亡率，缩短血管活性药物及有创机械通气使用时长，但仍需开展进一步研究以验证本研究结论，并明确重症监护场景下维生素C的最优给药剂量。
系统评价注册：https://www.crd.york.ac.uk/prospero/，标识符为CRD42022371090。