Department of Intensive Care Medicine, Amsterdam UMC, Location VUmc, Vrije Universiteit Amsterdam, Research VUmc Intensive Care (REVIVE), Amsterdam Medical Data Science (AMDS), Amsterdam Cardiovascular Science (ACS), Amsterdam Infection and Immunity Institute (AI&II), De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Department of Internal Medicine, Amsterdam UMC, Location VUmc, Vrije Universiteit Amsterdam, Research VUmc Intensive Care (REVIVE), Amsterdam Medical Data Science (AMDS), Amsterdam Cardiovascular Science (ACS), Amsterdam Infection and Immunity Institute (AI&II), De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Crit Care. 2019 Nov 21;23(1):366. doi: 10.1186/s13054-019-2658-4.
Crystalloids are the most frequently prescribed drugs in intensive care medicine and emergency medicine. Thus, even small differences in outcome may have major implications, and therefore, the choice between balanced crystalloids versus normal saline continues to be debated. We examined to what extent the currently accrued information size from completed and ongoing trials on the subject allow intensivists and emergency physicians to choose the right fluid for their patients.
Systematic review and meta-analysis with random effects inverse variance model. Published randomized controlled trials enrolling adult patients to compare balanced crystalloids versus normal saline in the setting of intensive care medicine or emergency medicine were included. The main outcome was mortality at the longest follow-up, and secondary outcomes were moderate to severe acute kidney injury (AKI) and initiation of renal replacement therapy (RRT). Trial sequential analyses (TSA) were performed, and risk of bias and overall quality of evidence were assessed. Additionally, previously published meta-analyses, trial sequential analyses and ongoing large trials were analysed for included studies, required information size calculations and the assumptions underlying those calculations.
Nine studies (n = 32,777) were included. Of those, eight had data available on mortality, seven on AKI and six on RRT. Meta-analysis showed no significant differences between balanced crystalloids versus normal saline for mortality (P = 0.33), the incidence of moderate to severe AKI (P = 0.37) or initiation of RRT (P = 0.29). Quality of evidence was low to very low. Analysis of previous meta-analyses and ongoing trials showed large differences in calculated required versus accrued information sizes and assumptions underlying those. TSA revealed the need for extremely large trials based on our realistic and clinically relevant assumptions on relative risk reduction and baseline mortality.
Our meta-analysis could not find significant differences between balanced crystalloids and normal saline on mortality at the longest follow-up, moderate to severe AKI or new RRT. Currently accrued information size is smaller, and the required information size is larger than previously anticipated. Therefore, completed and ongoing trials on the topic may fail to provide adequate guidance for choosing the right crystalloid. Thus, physiology will continue to play an important role for individualizing this choice.
晶体液是重症医学和急诊医学中最常使用的药物。因此，即使结果只有微小的差异，也可能会产生重大影响，因此，平衡晶体液与生理盐水之间的选择仍存在争议。我们研究了目前已完成和正在进行的关于该主题的试验所积累的信息量，以了解其在多大程度上可以让重症医师和急诊医师为患者选择正确的液体。
系统评价和随机效应逆方差模型的荟萃分析。纳入了比较重症医学或急诊医学环境中平衡晶体液与生理盐水的成年患者的随机对照试验。主要结局是最长随访时的死亡率，次要结局是中重度急性肾损伤（AKI）和开始肾脏替代治疗（RRT）。进行了试验序贯分析（TSA），并评估了偏倚风险和总体证据质量。此外，还分析了纳入研究的先前发表的荟萃分析、试验序贯分析和正在进行的大型试验，以获取所需信息的大小计算和这些计算的假设。
纳入了 9 项研究（n=32777）。其中 8 项研究有死亡率数据，7 项研究有 AKI 数据，6 项研究有 RRT 数据。荟萃分析显示，平衡晶体液与生理盐水相比，死亡率（P=0.33）、中重度 AKI 的发生率（P=0.37）或 RRT 的启动（P=0.29）均无显著差异。证据质量为低到极低。对先前的荟萃分析和正在进行的试验的分析表明，计算出的所需信息量与已积累信息量之间存在很大差异，且这些差异的假设也存在很大差异。基于我们对相对风险降低和基线死亡率的现实和临床相关假设，TSA 显示需要进行非常大的试验。
我们的荟萃分析未发现最长随访时间、中重度 AKI 或新 RRT 方面，平衡晶体液与生理盐水之间存在显著差异。目前已积累的信息量较小，所需信息量大于预期。因此，该主题已完成和正在进行的试验可能无法为选择正确的晶体液提供足够的指导。因此，生理学将继续在个体化选择中发挥重要作用。
