Elevated levels of endotoxin, oxygen-derived free radicals, and cytokines during extracorporeal membrane oxygenation.

It has been demonstrated that the initiation of extracorporeal membrane oxygenation (ECMO) is associated with an increase in the circulating plasma levels of inflammatory mediators. We have expanded the study of these substances to include measurements of complement activation, prostaglandin production, endotoxin appearance, oxygen-derived free radical generation, and cytokine release before, during, and after ECMO. A reproducible second phase of complement activity and prostaglandin synthesis was associated with the appearance of detectable circulating endotoxin (0.04 U/mL pre-ECMO to 0.07 U/mL at 36 hours, P less than .05). Oxygen-derived free radical activity also increased (2 ng/mL to 3 ng/mL at 36 hours, P less than .05), as did plasma levels of tumor necrosis factor (40 pg/mL to 70 pg/mL at 36 hours, nonsurvivor group: P less than .05). Interleukin-1 was elevated above normal, but there were no significant variations noted during the time period studied. Small amounts of interleukin-6 were also detected in the occasional patient. None of these mediators differed significantly between survivors and nonsurvivors. These data indicate that ECMO is associated with a previously undescribed, endotoxin-related, generalized inflammatory state after 36 hours of support. The pulmonary, renal, and cardiac dysfunctions documented with prolonged bypass can all be related to a classic sepsis syndrome.