Romaschin Alexander D, Klein David J, Marshall John C
Crit Care. 2012 Dec 3;16(6):248. doi: 10.1186/cc11495.
Endotoxin detection in human patients has been a difficult challenge, in part due to the fact that the conserved active portion of the molecule (lipid A) is a relatively small epitope only amenable to binding by a single ligand at any one instance and low levels (pg/ml) are capable of stimulating the immune system. The endotoxin activity assay, a bioassay based on neutrophil activation by complement opsonized immune complexes of lipopolysaccharide (LPS), has allowed the specific detection of the lipid A epitope of LPS in a rapid whole blood assay format. This review summarizes diagnostic studies utilizing the endotoxin activity assay in a variety of hospital patient populations in whom endotoxin is postulated to play a significant role in disease etiology. These include ICU patients at risk of developing 'sepsis syndrome', abdominal and cardiovascular surgery patients and patients with serious traumatic injury. Significant features of these studies include the high negative predictive value of the assay (98.6%) for rule out of Gram-negative infection, ability to risk stratify patients progressing to severe sepsis (odds ratio 3.0) and evidence of LPS release in patients with gut hypoperfusion. Preliminary studies have successfully combined the assay with anti-LPS removal strategies to prospectively identify patients who might benefit from this therapy with early evidence of clinical benefit.
在人类患者中检测内毒素一直是一项艰巨的挑战，部分原因在于该分子的保守活性部分（脂质A）是一个相对较小的表位，在任何一个时刻仅能与单个配体结合，而且低水平（皮克/毫升）就能刺激免疫系统。内毒素活性测定是一种基于脂多糖（LPS）补体调理免疫复合物激活中性粒细胞的生物测定法，它能以快速全血测定形式特异性检测LPS的脂质A表位。本综述总结了在各种医院患者群体中利用内毒素活性测定进行的诊断研究，这些患者群体中内毒素被认为在疾病病因中起重要作用。这些群体包括有发生“脓毒症综合征”风险的重症监护病房（ICU）患者、腹部和心血管手术患者以及严重创伤患者。这些研究的显著特点包括该测定法对排除革兰氏阴性菌感染的高阴性预测值（98.6%）、对进展为严重脓毒症患者进行风险分层的能力（优势比3.0）以及肠道灌注不足患者中LPS释放的证据。初步研究已成功将该测定法与抗LPS清除策略相结合，以前瞻性地识别可能从该治疗中获益的患者，并获得了早期临床获益的证据。
