Endotoxemia and acute-phase proteins in major abdominal surgery

Background: Translocation of endotoxin is a controversial issue. The abilit y of plasma to inactivate endotoxin is an indirect measure of endotoxemia. Endotoxin is a potent stimulator of the inflammatory response and affects t he innate immune system. Objective: To elucidate the kinetics of endotoxemia and the ability of plas ma to inactivate endotoxin in patients with major abdominal operations. To demonstrate the early time course of the acute-phase proteins C-reactive pr otein (CRP), serum amyloid A (SAA), alpha (1)-antitrypsin, alpha (2)-macrog lobulin, transferrin, and interleukin 6 (IL-6), and to correlate them with the amount of endotoxemia. Methods: Twenty patients with elective major abdominal operation and 10 hea lthy controls were investigated. Blood was collected preoperatively, during the operation and regularly up to 12 days after surgery. Endotoxin was mea sured by Limulus amebocyte lysate test (LAL), the ability of plasma to inac tivate endotoxin by modified LAL, the acute-phase proteins nephelometricall y, and IL-6 by enzyme-linked immunosorbent assay (ELISA). Results: Preoperative endotoxin plasma level (0.026 +/- 0.004 EU/mL) did no t differ from healthy volunteers but increased during operation (0.09 +/- 0 .02 EU/mL, P = 0.02). Endotoxemia peaked 1 hour after the surgical procedur e (0.16 +/- 0.03 EU/mL; P <0.0001 versus preoperative) and decreased to alm ost normal values after 48 hours. The capability of plasma to inactivate en dotoxin 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 op eration 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 surger y (470 +/- 108 pg/mL). CRP peaked at 210 +/- 19 mg/L (P <0.0001 versus preo perative) 48 hours after operation and was significantly elevated for the r est of the observation period. SAA was significantly increased 24 hours aft er surgery (249 +/- 45 mg/L) and peaked additional 48 hours later (456 +/- 86 mg/L). alpha (1)-Antitrypsin, although a positive acute-phase protein, d ecreased 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 (preo perative, 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 endotoxem ia 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 alph a (2)-macroglobulin (-0.53 > r > -0.6, P <0.05) as well as <alpha>(1)-antit rypsin (0.64 > r > 0.55, P <0.05) on the other. Conclusion: Major abdominal surgery is associated with transient endotoxemi a and a transient reduced endotoxin inactivation capacity of the plasma. En dotoxemia correlates with the endotoxin inactivation capacity. The surgical procedure causes substantial changes in plasma concentrations of acute-pha se proteins. <alpha>(2)-Macroglobulin and alpha (1)-antitrypsin correlate m oderately with endotoxemia. (C) 2001 Excerpta Medica, Inc. All rights reser ved.