Tegl Vaclav, Horak Jan, Nalos Lukas, Horakova Michala, Stengl Milan, Matejovic Martin, Benes Jan
Laboratory of Experimental Intensive Care Medicine, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, 323 00, Pilsen, Czech Republic.
Department of Anesthesiology, Resuscitation and Intensive Care, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
Intensive Care Med Exp. 2024 Apr 18;12(1):38. doi: 10.1186/s40635-024-00622-x.
The use of hemoadsorption (HA) has become popular in the treatment of vasoplegic states associated with massive cytokine release, including septic shock. However, this approach does not seem to be based on robust evidence, and it does not follow international guidelines. To understand the pathophysiological rationale and timing of HA, we conducted a large animal septic shock experiment.
Prospective randomized large-animal peritoneal septic shock experiment.
Laboratory investigation.
Twenty-six anesthetized, mechanically ventilated, and instrumented pigs randomly assigned into (1) sham-operated group with HA (SHAM, n = 5); (2) sepsis animals without HA (SEPSIS, n = 5); (3) sepsis group with HA at norepinephrine initiation (EARLY, n = 8); and (4) sepsis group with HA initiated at norepinephrine rate reaching 0.5 μg/kg/min (LATE, n = 8).
Peritoneal sepsis was induced by cultivated autologous feces inoculation. A CytoSorb cartridge (200 g) with a blood flow rate of 200 mL/min and heparin anticoagulation was used to perform HA. The animals received sedation and intensive organ support up to 48 h or until they experienced cardiovascular collapse.
Systemic hemodynamics, multiple-organ functions, and immune-inflammatory response were measured at predefined periods. The HA treatment was not associated with any measurable benefit in terms of systemic hemodynamics and organ support. The systemic inflammatory markers were unaffected by any of the treatment timings. In contrast, the HA resulted in higher vasopressor load and decreased 36-h survival (5 animals in SHAM (100%), 4 (80%) in SEPSIS, 4 (57%) in EARLY, and 2 (25%) in LATE; p = 0.041). The HA exposure in healthy animals was associated with hemodynamic deterioration, systemic inflammatory response, and cytopenia.
In this large-animal-controlled fulminant sepsis study, the HA was unable to counteract the disease progression in the early or advanced septic shock phase. However, findings from the HA-exposed sham animals suggest potential safety concerns.
血液吸附（HA）已广泛应用于治疗与大量细胞因子释放相关的血管麻痹状态，包括感染性休克。然而，这种治疗方法似乎缺乏有力证据支持，且未遵循国际指南。为了解HA的病理生理机制及应用时机，我们开展了一项大型动物感染性休克实验。
前瞻性随机大型动物腹腔感染性休克实验。
实验室研究。
26只麻醉、机械通气并安装监测仪器的猪，随机分为：（1）假手术HA组（SHAM，n = 5）；（2）未行HA的脓毒症动物组（SEPSIS，n = 5）；（3）去甲肾上腺素起始时行HA的脓毒症组（EARLY，n = 8）；（4）去甲肾上腺素剂量达到0.5 μg/kg/min时开始行HA的脓毒症组（LATE，n = 8）。
通过接种自体培养粪便诱导腹腔感染。使用血流速度为200 mL/min的CytoSorb柱（200 g）并采用肝素抗凝进行HA治疗。动物接受镇静及强化器官支持，持续48小时或直至出现心血管功能衰竭。
在预设时间点测量全身血流动力学、多器官功能及免疫炎症反应。HA治疗在全身血流动力学和器官支持方面未显示出任何可测量的益处。全身炎症标志物不受任何治疗时机的影响。相反，HA导致血管升压药使用量增加，36小时生存率降低（SHAM组5只（100%），SEPSIS组4只（80%），EARLY组4只（57%），LATE组2只（25%）；p = 0.041）。健康动物接受HA治疗与血流动力学恶化、全身炎症反应及血细胞减少有关。
在这项大型动物对照暴发性脓毒症研究中，HA无法在感染性休克的早期或晚期阶段对抗疾病进展。然而，HA处理的假手术动物的研究结果提示存在潜在安全问题。
