The objective was to test prospectively supranormal values of cardiac index (CI), oxygen delivery index (DO2I), and oxygen consumption index (VO2I) as resuscitation goals to improve outcome in severely traumatized patients. We included patients > or = 16 years of age who had either (1) an estimated blood loss > or = 2000 mL or (2) a pelvic fracture and/or two or more major long bone fractures with > or = four units of packed red cells given within six hours of admission. The protocol resuscitation goals were CI > or = 4.5 L/min/m2, DO2I > or = 670 mL/min/m2, and VO2I > or = 166 mL/min/m2 within 24 hours of admission. The control resuscitation goals were normal vital signs, urine output, and central venous pressure. The 50 protocol patients had a significantly lower mortality (9 of 50, 18% vs. 24 of 65, 37%) and fewer organ failures per patient (0.74 +/- 0.28 vs. 1.62 +/- 0.45) than did the 75 control patients. We conclude that increased CI, DO2I, and VO2I seen in survivors of severe trauma are primary compensations that have survival value; augmentation of these compensations compared to conventional therapy decreases mortality.