Buttenschoen K, Buttenschoen D C, Berger D, Vasilescu C, Schafheutle S, Goeltenboth B, Seidelmann M, Beger H G
Department of General Surgery, University of Ulm, Steinhoevelstrasse 9, D-89075, Ulm, Germany.
Am J Surg. 2001 Jan;181(1):36-43. doi: 10.1016/s0002-9610(00)00534-1.
Translocation of endotoxin is a controversial issue. The ability of plasma to inactivate endotoxin is an indirect measure of endotoxemia. Endotoxin is a potent stimulator of the inflammatory response and affects the innate immune system.
To elucidate the kinetics of endotoxemia and the ability of plasma to inactivate endotoxin in patients with major abdominal operations. To demonstrate the early time course of the acute-phase proteins C-reactive protein (CRP), serum amyloid A (SAA), alpha(1)-antitrypsin, alpha(2)-macroglobulin, transferrin, and interleukin 6 (IL-6), and to correlate them with the amount of endotoxemia.
Twenty patients with elective major abdominal operation and 10 healthy controls were investigated. Blood was collected preoperatively, during the operation and regularly up to 12 days after surgery. Endotoxin was measured by Limulus amebocyte lysate test (LAL), the ability of plasma to inactivate endotoxin by modified LAL, the acute-phase proteins nephelometrically, and IL-6 by enzyme-linked immunosorbent assay (ELISA).
Preoperative endotoxin plasma level (0.026 +/- 0.004 EU/mL) did not differ from healthy volunteers but increased during operation (0.09 +/- 0.02 EU/mL, P = 0.02). Endotoxemia peaked 1 hour after the surgical procedure (0.16 +/- 0.03 EU/mL; P <0.0001 versus preoperative) and decreased to almost normal values after 48 hours. The capability of plasma to inactivate endotoxin was significantly reduced during (recovery, 0.16 +/- 0.03 EU/mL), 1 hour (0.25 +/- 0.04 EU/mL) and 24 hours (0.16 +/- 0.02 EU/mL) after the operation compared with preoperative (0.068 +/- 0.01 EU/mL) values. Plasma IL-6 was significantly increased for 48 hours with a peak 1 hour after surgery (470 +/- 108 pg/mL). CRP peaked at 210 +/- 19 mg/L (P <0.0001 versus preoperative) 48 hours after operation and was significantly elevated for the rest of the observation period. SAA was significantly increased 24 hours after surgery (249 +/- 45 mg/L) and peaked additional 48 hours later (456 +/- 86 mg/L). alpha(1)-Antitrypsin, although a positive acute-phase protein, decreased initially to 1.38 +/- 0.1 g/L (preoperative, 2.33 +/- 0.18 g/L; P <0.0001) and increased thereafter until day 12 (3.05 +/- 0.35 g/L, P = 0.11 versus preoperative). The same was true for alpha(2)-macroglobulin (preoperative, 2.2 +/- 0.16 g/L; intraoperative, 1.36 +/- 0.13 g/L; day 5, 2.8 +/- 0.4 g/L). Transferrin decreased already during surgery (1.6 +/- 0.1 g/L versus preoperative 2.8 +/- 0.17 g/L, P <0.0001) and remained on this level for 5 days. Correlation analysis revealed a relationship between endotoxemia and the ability of plasma to inactivate endotoxin (r = 0.67, P <0.0001) and also a relation between intraoperative endotoxemia on one hand and alpha(2)-macroglobulin (-0.53 > r > -0.6, P <0.05) as well as alpha(1)-antitrypsin (0.64 > r >0.55, P <0.05) on the other.
Major abdominal surgery is associated with transient endotoxemia and a transient reduced endotoxin inactivation capacity of the plasma. Endotoxemia correlates with the endotoxin inactivation capacity. The surgical procedure causes substantial changes in plasma concentrations of acute-phase proteins. alpha(2)-Macroglobulin and alpha(1)-antitrypsin correlate moderately with endotoxemia.
内毒素移位是一个存在争议的问题。血浆对内毒素的灭活能力是内毒素血症的一种间接测量方法。内毒素是炎症反应的强效刺激物，会影响先天免疫系统。
阐明腹部大手术患者内毒素血症的动力学以及血浆对内毒素的灭活能力。展示急性期蛋白C反应蛋白（CRP）、血清淀粉样蛋白A（SAA）、α1抗胰蛋白酶、α2巨球蛋白、转铁蛋白和白细胞介素6（IL-6）的早期时间进程，并将它们与内毒素血症的量相关联。
对20例行择期腹部大手术的患者和10名健康对照者进行研究。在术前、手术期间以及术后定期直至术后12天采集血液。通过鲎试剂法（LAL）测量内毒素，通过改良LAL法测量血浆对内毒素的灭活能力，通过比浊法测量急性期蛋白，通过酶联免疫吸附测定（ELISA）法测量IL-6。
术前血浆内毒素水平（0.026±0.004 EU/mL）与健康志愿者无差异，但在手术期间升高（0.09±0.02 EU/mL，P = 0.02）。内毒素血症在手术操作后1小时达到峰值（0.16±0.03 EU/mL；与术前相比，P <0.0001），并在48小时后降至几乎正常水平。与术前（0.068±0.01 EU/mL）值相比，血浆对内毒素的灭活能力在术后（恢复时，0.16±0.03 EU/mL）、1小时（0.25±0.04 EU/mL）和24小时（0.16±0.02 EU/mL）时显著降低。血浆IL-6在48小时内显著升高，在术后1小时达到峰值（470±108 pg/mL）。CRP在术后48小时达到峰值210±19 mg/L（与术前相比，P <0.0001），并在其余观察期内显著升高。SAA在术后24小时显著升高（249±45 mg/L），并在另外48小时后达到峰值（456±86 mg/L）。α1抗胰蛋白酶虽然是一种阳性急性期蛋白，但最初降至1.38±0.1 g/L（术前为2.33±0.18 g/L；P <0.0001），此后升高直至第12天（3.05±0.35 g/L，与术前相比，P = 0.11）。α2巨球蛋白情况相同（术前为2.2±0.16 g/L；术中为1.36±0.13 g/L；第5天为2.8±0.4 g/L）。转铁蛋白在手术期间已经降低（1.6±0.1 g/L，术前为2.8±0.17 g/L，P <0.0001），并在该水平维持5天。相关性分析显示内毒素血症与血浆对内毒素的灭活能力之间存在关系（r = 0.67，P <0.0001），并且术中内毒素血症一方面与α2巨球蛋白（-0.53 > r > -0.6，P <0.05）以及α1抗胰蛋白酶（0.64 > r >0.55，P <0.05）另一方面之间也存在关系。
腹部大手术与短暂的内毒素血症以及血浆对内毒素灭活能力的短暂降低有关。内毒素血症与内毒素灭活能力相关。手术操作导致急性期蛋白血浆浓度发生显著变化。α2巨球蛋白和α1抗胰蛋白酶与内毒素血症中度相关。
