OBJECTIVE: To study whether a reduction of the endotoxin load, once a generalized inflammatory state has been established, reduces the inflammatory response and endotoxin-induced effects on circulation, hypoperfusion, and organ dysfunction. DESIGN: Prospective parallel-grouped placebo-controlled randomized interventional experimental study. SETTING: University research unit. SUBJECTS: Healthy pigs. INTERVENTIONS: The animals were subjected to a continuous endotoxin infusion rate of either 4.0 or 0.063 microg endotoxin x kg x h for 1, 2, or 6 hours. The 1- and 2-hour infusion groups represented the applied therapy by a reduction of the endotoxin load of 5/6 and 2/3, respectively. MEASUREMENTS AND MAIN RESULTS: During a 6-hour experiment, laboratory and physiologic parameters were recorded hourly in 26 anesthetized and mechanically ventilated pigs. Primary end point was to detect differences in tumor necrosis factor-alpha (TNF-alpha) concentration during the last 3 hours of the experiment. Despite the early reduction of the endotoxin load, no effect on TNF-alpha concentration was observed. Similarly, in circulatory parameters, such as mean arterial pressure and oxygen delivery, and in platelet count and renal function, no effects were noted. However, there was some improvement in pulmonary compliance and function as determined by Pao2, Paco2, and pH. These changes were associated with slight improvements in leukocyte response and capillary leakage. CONCLUSIONS: Termination of the endotoxin infusion represents an incontestable model of endotoxin concentration reduction. Endotoxin elimination strategies applied at the TNF-alpha peak or later will have very little or no effect on TNF-alpha-mediated toxicity. Nevertheless, there was an effect on the leukocyte response that was associated with an improvement in respiratory function and microcirculation, making it impossible to rule out fully the beneficial effect of this strategy. However, the effects were limited in relation to the magnitude of the endotoxin concentration reduction and the very early application of the antiendotoxin measure.
OBJECTIVE: To study whether a reduction of the endotoxin load, once a generalized inflammatory state has been established, reduces the inflammatory response and endotoxin-induced effects on circulation, hypoperfusion, and organ dysfunction. DESIGN: Prospective parallel-grouped placebo-controlled randomized interventional experimental study. SETTING: University research unit. SUBJECTS: Healthy pigs. INTERVENTIONS: The animals were subjected to a continuous endotoxin infusion rate of either 4.0 or 0.063 microg endotoxin x kg x h for 1, 2, or 6 hours. The 1- and 2-hour infusion groups represented the applied therapy by a reduction of the endotoxin load of 5/6 and 2/3, respectively. MEASUREMENTS AND MAIN RESULTS: During a 6-hour experiment, laboratory and physiologic parameters were recorded hourly in 26 anesthetized and mechanically ventilated pigs. Primary end point was to detect differences in tumor necrosis factor-alpha (TNF-alpha) concentration during the last 3 hours of the experiment. Despite the early reduction of the endotoxin load, no effect on TNF-alpha concentration was observed. Similarly, in circulatory parameters, such as mean arterial pressure and oxygen delivery, and in platelet count and renal function, no effects were noted. However, there was some improvement in pulmonary compliance and function as determined by Pao2, Paco2, and pH. These changes were associated with slight improvements in leukocyte response and capillary leakage. CONCLUSIONS: Termination of the endotoxin infusion represents an incontestable model of endotoxin concentration reduction. Endotoxin elimination strategies applied at the TNF-alpha peak or later will have very little or no effect on TNF-alpha-mediated toxicity. Nevertheless, there was an effect on the leukocyte response that was associated with an improvement in respiratory function and microcirculation, making it impossible to rule out fully the beneficial effect of this strategy. However, the effects were limited in relation to the magnitude of the endotoxin concentration reduction and the very early application of the antiendotoxin measure.
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