Poeze M, Froon A H, Ramsay G, Buurman W A, Greve J W
Department of Surgery, University Hospital Maastricht, The Netherlands.
Shock. 2000 Oct;14(4):421-8. doi: 10.1097/00024382-200014040-00001.
Sepsis and organ failure remain the main cause of death on the ICU. Sepsis is characterized by a severe inflammatory response, in which platelet-activating factor (PAF) is considered to play an important role. This study investigated whether treatment with the PAF-antagonist TCV-309 reduces morbidity and mortality in patients with septic shock. The study was conducted as a double-blind, randomized, placebo controlled multicenter study. The included patients had to fulfill the SIRS criteria with a clinical suspicion of infection, an admission APACHE II score greater than 15, and shock, defined as a mean arterial pressure <70 mmHg and/or a decrease > or =40 mmHg despite adequate fluid resuscitation. Patients received 1.0 mg/kg TCV-309 or placebo, twice daily, intravenously during 14 days. The prospectively set goals were MOF score, recovery from shock, mortality, and assessment of the safety of the medication. A total of 98 patients were included of which 97 were analyzed on an intention-to-treat basis. The overall survival at day 56 of TCV-309 treated patients was similar compared to placebo treated patients (51.0% vs. 41.7%, P = 0.47). In contrast, the mean percentage of failed organs per patient present after 14 days in the TCV-309 treated patients was significantly lower compared to the placebo treated patients (11.9% vs. 25.1%, P = 0.04), leading to a reduced need for vasopressors, dialysis, and ventilatory support. Furthermore, the mean APACHE-II score during treatment with TCV-309 was significantly lower and the number of patients recovered from shock after day 14 was significantly higher in the TCV-309 treated patient group (2/32 vs. 9/29, P = 0.01). The number of adverse events was not significantly different between the TCV-309 and placebo treated patients. TCV-309 did not change overall mortality of septic shock, however a substantial reduction in organ dysfunction and morbidity, frequently associated with septic shock was achieved, without significant adverse events.
脓毒症和器官衰竭仍是重症监护病房（ICU）的主要死亡原因。脓毒症的特征是严重的炎症反应，其中血小板活化因子（PAF）被认为起重要作用。本研究调查了PAF拮抗剂TCV-309治疗是否能降低感染性休克患者的发病率和死亡率。该研究作为一项双盲、随机、安慰剂对照的多中心研究进行。纳入的患者必须符合全身炎症反应综合征（SIRS）标准，临床上怀疑有感染，入院急性生理与慢性健康状况评分系统（APACHE II）得分大于15，且有休克表现，定义为平均动脉压<70 mmHg和/或尽管进行了充分的液体复苏但血压下降≥40 mmHg。患者接受1.0 mg/kg TCV-309或安慰剂治疗，每日两次，静脉注射，持续14天。预先设定的目标是多器官功能障碍（MOF）评分、休克恢复情况、死亡率以及药物安全性评估。共纳入98例患者，其中97例按意向性分析原则进行分析。TCV-309治疗组患者在第56天的总体生存率与安慰剂治疗组相似（51.0%对41.7%，P = 0.47）。相比之下，TCV-309治疗组患者在14天后每个患者出现功能衰竭器官的平均百分比显著低于安慰剂治疗组（11.9%对25.1%，P = 0.04），从而减少了对血管升压药、透析和通气支持的需求。此外，TCV-309治疗组患者在治疗期间的平均APACHE-II评分显著更低，且在第14天后从休克中恢复的患者数量显著更多（2/32对9/29，P = 0.01）。TCV-309治疗组和安慰剂治疗组之间不良事件的数量没有显著差异。TCV-309并未改变感染性休克的总体死亡率，然而，它实现了与感染性休克相关的器官功能障碍和发病率的大幅降低，且没有明显的不良事件。
