Mechanical ventilation worsens abdominal edema and inflammation in porcine endotoxemia

Abstract

Introduction: We hypothesized that mechanical ventilation per se increases abdominal edema and inflammation in sepsis and tested this in experimental endotoxemia. Methods: Thirty anesthetized piglets were allocated to one of five groups: healthy control pigs breathing spontaneously with continuous positive pressure of 5 cm H2O or mechanically ventilated with positive end-expiratory pressure of 5 cm H2O, and endotoxemic piglets during mechanical ventilation for 2.5 hours and then continued on mechanical ventilation with positive end-expiratory pressure of either 5 or 15 cm H2O or switched to spontaneous breathing with continuous positive pressure of 5 cm H2O for another 2.5 hours. Abdominal edema formation was estimated by isotope technique, and inflammatory markers were measured in liver, intestine, lung, and plasma. Results: Healthy controls: 5 hours of spontaneous breathing did not increase abdominal fluid, whereas mechanical ventilation did (Normalized Index increased from 1.0 to 1.6; 1 to 3.3 (median and range, P < 0.05)). Endotoxemic animals: Normalized Index increased almost sixfold after 5 hours of mechanical ventilation (5.9; 4.9 to 6.9; P < 0.05) with twofold increase from 2.5 to 5 hours whether positive end-expiratory pressure was 5 or 15, but only by 40% with spontaneous breathing (P < 0.05 versus positive end-expiratory pressure of 5 or 15 cm H2O). Tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in intestine and liver were 2 to 3 times higher with mechanical ventilation than during spontaneous breathing (P < 0.05) but similar in plasma and lung. Abdominal edema formation and TNF-α in intestine correlated inversely with abdominal perfusion pressure. Conclusions: Mechanical ventilation with positive end-expiratory pressure increases abdominal edema and inflammation in intestine and liver in experimental endotoxemia by increasing systemic capillary leakage and impeding abdominal lymph drainage. © 2013 Lattuada et al.; licensee BioMed Central Ltd.