Hyperdynamic Sepsis Modifies a PEEP-mediated Redistribution in Organ Blood Flows

Abstract

Changes in organ blood flow (Q) produced by 20 cm H2O positive end-expiratory pressure (PEEP) were measured before and after the induction of hyperdynamic sepsis in nine unanesthetized sheep. During the baseline nonseptic study, PEEP was associated with a 9% fall in thermodilution-measured systemic Q, although arterial perfusing pressures were unaffected. Concurrently, microsphere-derived Q was maintained to the brain and heart, but fell to liver, spleen, pancreas, kidney, large intestine, and gastrocnemius. Twenty-four to 36 h after cecal ligation and perforation, a pre-PEEP septic study demonstrated an increase in all of the cardiac index (CI) (+43%) and systemic O2 delivery (+54%) when compared with the nonseptic study, whereas whole-body O2 extraction (-30%) was depressed. Although PEEP depressed systemic Q (-17%) during the septic study to a greater extent than during the nonseptic study (p less than 0.02), absolute organ Q fell only to pancreas, liver, and spleen. Relative to the simultaneous fall in the CI, Q to some splanchnic organs was not depressed by PEEP to the same magnitude in the septic as in the nonseptic study. When an infusion of Ringer's lactate (993 +/- 295 ml) subsequently restored systemic Q to pre-PEEP septic levels, individual flows that had been depressed by PEEP were not restored. Furthermore, Q-kidney continued to fall, such that the postfluid Q-kidney (-19%) was significantly less than was demonstrated in the pre-PEEP septic study. We postulate that differences noted in the distribution of organ Q between the nonseptic and hyperdynamic septic studies after the application of PEEP were secondary to the vasculopathy of sepsis and/or an alteration in the function of specific organ microcirculations. However, these data do not address whether the changes in organ Q distribution after a PEEP-mediated depression in systemic Q during sepsis significantly restricted tissue DO2. The inability to acutely reverse the PEEP-mediated changes in organ Q after restoring systemic Q by a fluid infusion also suggests the need to evaluate alternative methods of support to organ Q in acute respiratory failure secondary to sepsis when the addition of PEEP acutely depresses systemic DO2.