Hemodynamic, metabolic, and organ function effects of pure oxygen ventilation during established fecal peritonitis-induced septic shock

Objective: To test the hypothesis whether pure oxygen ventilation is equally safe and beneficial in fully developed fecal peritonitis-induced septic shock as hyperoxia initiated at the induction of sepsis. Design: Prospective, randomized, controlled, experimental study with repeated measures. Setting: Animal research laboratory at a university medical school. Subjects. Twenty anesthetized, mechanically ventilated, and instrumented pigs. Interventions. Twelve hours after induction of fecal peritonitis by inoculation of autologous feces, swine, which were resuscitated with hydroxyethyl starch and norepinephrine to maintain mean arterial pressure at baseline values, were ventilated randomly with an FIO(2), required to keep Sao(2) > 90% (controls: n = 10) or FIO(2) 1.0 (hyperoxia, n = 10) during the next 12 hrs. Measurements and Main Results: Despite similar hemodynamic support (hydroxyethyl starch and norepinephrine doses), systemic and regional macrocirculatory and oxygen transport parameters, hyperoxia attenuated pulmonary hypertension, improved gut microcirculation (ileal mucosal laser Doppler flowmetry) and portal venous acidosis, prevented the deterioration in creatinine clearance (controls 61-(44;112), hyperoxia: 96 (88;110) mL.min(-1), p = .074), and attenuated the increase in blood tumor necrosis factor-a. concentrations (p = .045 and p = .112 vs. controls at 18 hrs and 24 hrs, respectively). Lung and liver histology (hematoxyline eosine staining) were comparable in the two groups, but hyperoxia reduced apoptosis (Tunel test) in the liver (4 (3;8) vs. 2 (1;5) apoptotic cells/field, p = .069) and the lung (36 (31;46) vs. 15 (13;17) apoptotic cells/field, p < .001). Parameters of lung function, tissue antioxidant activity, blood oxidative and nitrosative stress (nitrate + nitrite, 8-isoprostane levels; deoxyribonucleic acid (DNA) damage measured using the comet assay) were not further affected during hyperoxia. Conclusions. When compared with the previous report on hyperoxia initiated simultaneously with induction of sepsis, i.e., using a pretreatment approach, pure oxygen ventilation started when porcine fecal peritonitis-induced septic shock was fully developed proved to be equally safe with respect to lung function and oxidative stress, but exerted only moderate beneficial effects. (Crit Care Med 2009; 37:2465-2469)