Effect of fibronectin-rich human cryoprecipitate on fluid volume requirements in sheep during postoperative sepsis

Septic surgical patients often require fluid administration to maintain cardiovascular stability due, in part, to the sepsis-induced increase in vascular permeability and associated plasma volume depletion. Plasma fibronectin deficiency exists in such septic patients. We determined if maintenance of fibronectin levels by administration of fibronectin-rich human plasma cryoprecipitate would lower the resuscitative fluid volume needed for support of arterial pressure in septic postoperative sheep which were experimentally depleted of plasma fibronectin. Following a 2-hr postoperative baseline period, denatured collagen (gelatin, 8.7 mg/kg), which has a high affinity for fibronectin, was infused into both control and experimental sheep in order to acutely deplete plasma fibronectin. Sheep were then challenged both intraperitoneally and intravenously with live Pseudomonas (5 x 10(10) bacteria IP; 5 x 10(9) bacteria IV). Experimentals were given fresh plasma cryoprecipitate intravenously at a dose of 4 units bolus, followed by 3 units/hr for 5 hr. Controls received plasma cryoprecipitate selectively depleted of fibronectin by affinity chromatography. Bacterial challenge rapidly resulted in severe systemic hypotension. Ringer's lactate was infused intravenously into both groups at a rate sufficient to maintain a systemic arterial pressure of approximately 50 mm Hg with a maximum pulmonary artery wedge pressure of 15-18 mm Hg. Its rate of infusion was periodically adjusted to maintain this hemodynamic status. Comparison was made of the volume of Ringer's lactate required to maintain an arterial pressure of 50 mm Hg in both groups. Net fluid requirement was significantly (p less than 0.05) less in postoperative septic sheep (47.4 +/- 6.2 mg/kg/hr) treated with fibronectin-rich cryoprecipitate compared to the fluid requirement (71.7 +/- 4.7 mg/kg/hr) for postoperative septic sheep receiving fibronectin-deficient cryoprecipitate. Thus elevation of plasma fibronectin concentration lowers the fluid requirements needed for hemodynamic support in postoperative Gram-negative sepsis.