Elimination of glutamate using CRRT for 72 h in patients with post-cardiac arrest syndrome: A randomized clinical pilot trial

Elimination of glutamate using CRRT for 72 h in patients with post-cardiac arrest syndrome: A randomized clinical pilot trial
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DOI:
10.1016/j.resuscitation.2019.09.020
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发表时间:
2019-11-01
期刊:
影响因子:
6.5
通讯作者:
Storm, Christian
Storm, Christian
中科院分区:
医学2区
文献类型:
--
作者:
Nee, Jens;Joerres, Achim;Storm, Christian

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目的:谷氨酰胺和谷氨酸是心脏骤停后综合征期间继发性脑细胞死亡的主要介质。由于脑组织和血浆中谷氨酰胺和谷氨酸浓度之间存在平衡,通过体外血液净化将它们从体循环中消除可能最终导致大脑中继发性细胞死亡的减少。我们假设通过连续静脉静脉血液透析滤过 (CVVHDF) 可以显着降低全身谷氨酰胺和谷氨酸盐。方法:这是一项针对心脏骤停后幸存者的前瞻性、随机临床试验,评估入院后 72 小时内的护理标准或额外 CVVHDF。对两组的八个时间点的谷氨酰胺和谷氨酸血浆浓度进行分析。主要终点是谷氨酰胺和谷氨酸血浆浓度的降低。该试验已在临床试验中注册。 gov (NCT02963298)。结果:总共 41 名患者在 12 个月内被随机分配(对照 n = 21,CVVHDF n = 20)。 CVVHDF 降低谷氨酰胺和谷氨酸血浆浓度的主要目标并未实现;在研究期间,两组的浓度均维持在正常范围内(谷氨酸:4.7-11.1 mg/dL;谷氨酰胺:0.2-3.7 mg/dL)。然而,CRRT 患者过滤后谷氨酰胺和谷氨酸浓度与过滤前浓度相比显着降低(谷氨酸:过滤前中位数 8.85 mg/dL IQR 7.1-9.6;过滤后 0.95 mg/dL IQR 0.5 -2;p < 0.001;谷氨酰胺:过滤前 0.7 mg/dL IQR 0.6-1;过滤后 0.2 mg/dL IQR 0-0.2;p < 0.001)。结论:在本试验中,CVVHDF 无法显着降低全身血浆谷氨酰胺和谷氨酸水平。心脏骤停后患者的血浆谷氨酰胺和谷氨酸水平在正常范围内。
Aim: Glutamine and glutamate are major mediators of secondary brain cell death during post-cardiac arrest syndrome. As there is an equilibrium between brain tissue and plasma concentrations of glutamine and glutamate, their elimination from systemic circulation by extracorporeal blood purification may ultimately lead to reduced secondary cell death in the brain. We hypothesized that systemic glutamine and glutamate can be significantly reduced by continuous venovenous hemodiafiltration (CVVHDF).Methods: This was a prospective, randomized clinical trial in post cardiac-arrest survivors evaluating standard of care or additional CVVHDF over 72 h immediately after admission. Glutamine and glutamate plasma concentrations were analyzed at eight time points in both groups. Primary endpoint was reduction of glutamine and glutamate plasma concentrations. The trial has been registered at clinical trial. gov (NCT02963298).Results: In total, 41 patients were randomized over a period of 12 months (control n = 21, CVVHDF n = 20). The primary aim reduction of glutamine and glutamate plasma concentrations by CVVHDF, was not achieved; both groups-maintained concentrations within a normal range over the study period (glutamate: 4.7-11.1 mg/dL; glutamine: 0.2-3.7 mg/dL). However, post-filter concentrations of glutamine and glutamate in CRRT patients were significantly decreased as compared to pre-filter concentrations (glutamate: pre-filter median 8.85 mg/dL IQR 7.1-9.6; post-filter 0.95 mg/dL IQR 0.5 -2; p < 0.001; glutamine: pre-filter 0.7 mg/dL IQR 0.6-1; post-filter 0.2 mg/dL IQR 0-0.2; p < 0.001).Conclusion: In this trial, CVVHDF was not able to statistically significantly lower systemic plasma glutamine and glutamate levels. Post-cardiac arrest patients had plasma glutamine and glutamate levels within the normal range.