Plasma Resuscitation Improved Survival in a Cecal Ligation and Puncture Rat Model of Sepsis

Background: The paradigm shift from crystalloid to plasma resuscitation of traumatic hemorrhagic shock has improved patient outcomes due in part to plasma-mediated reversal of catecholamine and inflammation-induced endothelial injury, decreasing vascular permeability and attenuating organ injury. Since sepsis induces a similar endothelial injury as seen in hemorrhage, we hypothesized that plasma resuscitation would increase 48-h survival in a rat sepsis model. Methods: Adult male Sprague-Dawley rats (375-425 g) were subjected to 35% cecal ligation and puncture (CLP) (t = 0 h). Twenty-Two hours post-CLP and prior to resuscitation (t = 22 h), animals were randomized to resuscitation with normal saline (NS, 10 cc/kg/h) or pooled rat fresh frozen plasma (FFP, 3.33 cc/kg/h). Resuscitation under general anesthesia proceeded for the next 6 h (t = 22 h to t = 28 h); lactate was checked every 2 h, and fluid volumes were titrated based on lactate clearance. Blood samples were obtained before (t = 22 h) and after resuscitation (t = 28 h), and at death or study conclusion. Lung specimens were obtained for calculation of wet-To-dry weight ratio. Fisher exact test was used to analyze the primary outcome of 48-h survival. ANOVA with repeated measures was used to analyze the effect of FFP versus NS resuscitation on blood gas, electrolytes, blood urea nitrogen (BUN), creatinine, interleukin (IL)-6, IL-10, catecholamines, and syndecan-1 (marker for endothelial injury). A two-Tailed alpha level of <0.05 was used for all statistical tests. Results: Thirty-Three animals were studied: 14 FFP, 14 NS, and 5 sham. Post-CLP but preresuscitation (t = 22 h) variables between FFP and NS animals were similar and significantly deranged compared with sham animals. FFP significantly increased 48-h survival compared to NS (n = 8 [57%] vs n = 2 [14%]), attenuated the post-resuscitation (t = 28 h) levels of epinephrine (mean 2.2 vs 7.0 ng/mL), norepinephrine, (3.8 vs 8.9 ng/mL), IL-6 (3.8 vs 18.7 ng/mL), and syndecan-1 (21.8 vs 31.0 ng/mL) (all P < 0.05), improved the post-resuscitation PO 2 to FiO 2 ratio (353 vs 151), and reduced the pulmonary wet-To-dry weight ratio (5.28 vs 5.94) (all P < 0.05). Conclusion: Compared to crystalloid, plasma resuscitation increased 48-h survival in a rat sepsis model, improved pulmonary function and decreased pulmonary edema, and attenuated markers for inflammation, endothelial injury, and catecholamines.