METHODS Small-volume resuscitation by means of bolus application of hypertonic saline solutions has been demonstrated to restore central hemodynamics and regional blood flow in severe hemorrhagic and traumatic shock. The aim of this study was to elucidate the potential of this new concept for treatment of profound hypovolemia and microcirculatory deterioration associated with sepsis and endotoxic shock. In a porcine model of acute hyperdynamic endotoxemia (elicited by continuous iv infusion of Salmonella abortus equi endotoxin for 3.5 hrs), small-volume resuscitation applying hypertonic-hyperoncotic solutions was analyzed for its effect on central hemodynamics, oxygen delivery (Do2), and regional blood flow. Fluid therapy was initiated when the pulmonary artery occlusion pressure (PAOP) tended to decrease (at 43 to 52 mins of endotoxemia), and consisted of 4 mL/kg bolus infusion of either 7.2% sodium chloride, 10% dextran, or 10% dextran in 7.2% sodium chloride; thereafter, PAOP was maintained by controlled infusion of 6% dextran-60. In a control group, 6% dextran-60 was given without preinjection of hypertonic-hyperoncotic solutions. RESULTS On small-volume resuscitation, cardiac index significantly increased within 5 mins in all groups, while mean arterial pressure remained unchanged. Fluid requirements were significantly reduced after small-volume resuscitation and the hyperdynamic circulatory state was maintained until the end of the observation period; Do2 as well as blood flow to heart, kidneys, and splanchnic organs remained high. CONCLUSIONS Small-volume resuscitation by means of hypertonic saline-dextran proved the most effective, and seems to be an attractive supportive therapy to prevent microcirculatory failure in sepsis and endotoxemia.