Successful resuscitation of the injured may be achieved more rapidly and with less fluid using hypertonic crystalloid solutions than with isotonic solutions. This randomized, double-blind study compared 0.9% normal saline (NS) to 1.8% hypertonic saline (HS) in 20 postoperative coronary artery bypass patients suffering uniform injury. Study solutions were administered to maintain physiologic endpoints: heart rate, blood pressure, and pulmonary capillary wedge pressure. The groups were similar with respect to age, body surface area, operative procedure, intraoperative fluid status, and intraoperative and postoperative red cell transfusion requirements. HS patients required 30% less fluid than NS patients and were in negative fluid balance during the study (-1,715 +/- 732 ml/24 hr, HS, vs. +266 +/- 825 ml/24 hr, NS; p less than 0.01). In contrast, NS patients were in positive fluid balance after 8 hours. Moreover, HS patients experienced less chest tube drainage than NS patients (981 +/- 88 ml, HS, vs. 1,700 +/- 285 ml, NS; p less than 0.01). Systemic and pulmonary hemodynamic measurements, oxygen delivery, oxygen consumption, and shunt fraction did not differ between the two groups. Serum sodium and osmolality increased in the HS group and peaked at 12 hours (145.4 +/- 1.4 mEq/L and 308.7 +/- 2.0 mOsm/kg, respectively) and correlated with the volume of HS infused (correlation coefficient = 0.81). No deaths occurred and no complication was attributed the hypertonicity of the solution. We conclude that 1.8% hypertonic saline is a safe alternative to isotonic crystalloid therapy in the fluid management of postoperative patients. Decreased third-space losses may occur with HS as suggested by the lower thoracic losses in the HS group; 1.8% NaCl may be the preferred solution in situations where excess free water administration is not desired, and where interstitial edema is detrimental to function and/or survival.