Molinari Luca, Tidswell Mark A, Al-Khafaji Ali, Davison Danielle, Galphin Claude, Kamaluddin Esha, Foster Debra M, Kellum John A
Department of Translational Medicine, Università degli Studi del Piemonte Orientale, Novara, Italy.
Division of Pulmonary and Critical Care Medicine, Baystate Medical Center, Springfield, MA.
Crit Care Explor. 2025 Aug 28;7(9):e1308. doi: 10.1097/CCE.0000000000001308. eCollection 2025 Sep 1.
The relationship between endotoxin activity, organ failure, and mortality is not well understood.
To test whether the combination of endotoxin activity and organ failure identifies patients at higher risk of death from sepsis and determine the relationship to previously described sepsis phenotypes.
DESIGN, SETTING, AND PARTICIPANTS: Prospective observational study in four ICUs enrolling critically ill patients with septic shock.
Endotoxin activity assay (EAA) results, Sequential Organ Failure Assessment (SOFA), and multiple organ dysfunction (MODS) and 28-day mortality.
We enrolled 90 patients aged 25-95 years and set an EAA cutoff of greater than or equal to 0.6 together with SOFA greater than 11 or MODS greater than 9 to define endotoxic septic shock (ESS). At baseline mean EAA was 0.64 (sd = 0.19), whereas mean SOFA and MODS were 10.3 (sd 3.2) and 5.8 (sd 3.1), respectively. EAA greater than or equal to 0.6 and SOFA greater than 11 were present in 20 patients (23.3%) and these patients had 60% mortality. EAA greater than or equal to 0.6 and SOFA less than or equal to 11 occurred in 31 (36.0%) with mortality 12.9%. Of the 35 remaining patients with EAA less than 0.6, 29 (33.7%) had SOFA less than or equal to 11 and 5 of them (17.2%) died. Only six patients (7.0%) had EAA less than 0.6 and SOFA greater than 11 and none died (p < 0.001). All patients with MODS greater than 9 also had EAA greater than or equal to 0.6 (12 patients) with 75% mortality. EAA greater than or equal to 0.6 with MODS less than or equal to 9 occurred in 39 patients with 17.9% mortality (p < 0.001). ESS (EAA ≥ 0.6 together with SOFA > 11 or MODS > 9) occurred in 21 patients and they had significantly higher mortality (57.1% vs. 15.9%, p < 0.001) compared with non-ESS, with a relative risk for death of 3.58 (95% CI, 1.86-6.91). Among ESS patients, 7 (33.3%) had δ phenotype, whereas only 4 (5.8%) had δ among non-ESS (p = 0.001).
ESS compromises patients with the highest mortality rate from sepsis. Such patients are most appropriate for trials testing anti-endotoxin therapy for improving survival.
内毒素活性、器官衰竭和死亡率之间的关系尚未完全明确。
检验内毒素活性与器官衰竭相结合是否能识别出脓毒症死亡风险较高的患者，并确定其与先前描述的脓毒症表型的关系。
设计、设置和参与者：在四个重症监护病房（ICU）进行的前瞻性观察研究，纳入患有感染性休克的重症患者。
内毒素活性测定（EAA）结果、序贯器官衰竭评估（SOFA）、多器官功能障碍（MODS）以及28天死亡率。
我们纳入了90名年龄在25至95岁之间的患者，将EAA临界值设定为大于或等于0.6，同时将SOFA大于11或MODS大于9定义为内毒素性感染性休克（ESS）。基线时，平均EAA为0.64（标准差=0.19），而平均SOFA和MODS分别为10.3（标准差3.2）和5.8（标准差3.1）。20名患者（23.3%）的EAA大于或等于0.6且SOFA大于11，这些患者的死亡率为60%。31名患者（36.0%）的EAA大于或等于0.6且SOFA小于或等于11，死亡率为12.9%。在其余35名EAA小于0.6的患者中，29名（33.7%）的SOFA小于或等于11，其中5名（17.2%）死亡。只有6名患者（7.0%）的EAA小于0.6且SOFA大于11，无一例死亡（p<0.001）。所有MODS大于9的患者EAA也均大于或等于0.6（12名患者），死亡率为75%。39名患者的EAA大于或等于0.6且MODS小于或等于9，死亡率为17.9%（p<0.001）。21名患者发生了ESS（EAA≥0.6且SOFA>11或MODS>9），与非ESS患者相比，他们的死亡率显著更高（57.1%对15.9%，p<0.001），死亡相对风险为3.58（95%置信区间，1.86 - 6.91）。在ESS患者中，7名（33.3%）具有δ表型，而非ESS患者中只有4名（5.8%）具有δ表型（p = 0.001）。
ESS患者脓毒症死亡率最高。这类患者最适合进行旨在改善生存的抗内毒素治疗试验。
