Endotoxemia and acute-phase proteins in major abdominal surgery

Abstract

Background: 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. Objective: 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), α 1-antitrypsin, α 2-macroglobulin, 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 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). Results: 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). α 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 α 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 α 2-macroglobulin (−0.53 > r > −0.6, P <0.05) as well as α 1-antitrypsin (0.64 > r >0.55, P <0.05) on the other. Conclusion: 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. α 2-Macroglobulin and α 1-antitrypsin correlate moderately with endotoxemia.