A TRIAL OF GOAL-ORIENTED HEMODYNAMIC THERAPY IN CRITICALLY ILL PATIENTS

Background. Hemodynamic therapy to raise the cardiac index and oxygen delivery to supranormal levels may improve outcomes in critically ill patients. We studied whether increasing the cardiac index to a supranormal level (cardiac-index group) or increasing mixed venous oxygen saturation to a normal level (oxygen-saturation group) would decrease morbidity and mortality among critically ill patients, as compared with a control group in which the target was a normal cardiac index. Methods. A total of 10,726 patients in 56 intensive care units were screened, among whom 762 patients belonging to predefined diagnostic categories with acute physiology scores of 11 or higher were randomly assigned to the three groups (252 to the control group, 253 to the cardiac-index group, and 257 to the oxygen-saturation group). Results. The hemodynamic targets were reached by 94.3 percent of the control group, 44.9 percent of the cardiac-index group, and 66.7 percent of the oxygen-saturation group (P 0.001). Mortality was 48.4, 48.6, and 52.1 percent, respectively (P 0.638), up to the time of discharge from the intensive care unit and 62.3, 61.7, and 63.8 percent (P 0.875) at six months. Among patients who survived, the number of dysfunctional organs and the length of the stay in the intensive care unit were similar in the three groups. No differences in mortality among the three groups were found for any diagnostic category. A subgroup analysis of the patients in whom hemodynamic targets were reached revealed similar mortality rates: 44.8, 40.4, and 39.0 percent, respectively (P 0.478). Conclusions. Hemodynamic therapy aimed at achieving supranormal values for the cardiac index or normal values for mixed venous oxygen saturation does not reduce morbidity or mortality among critically ill patients. (N Engl J Med 1995;333:1025-32.) From the Istituto di Anestesia e Rianimazione, Università di Milano, Ospedale Maggiore di Milano, Istituto di Ricovero e Cura a Carattere Scientifico, Milan (L.G., L.B., P.P.); the Istituto di Ricerche Farmacologiche “Mario Negri,” Milan (R.L., G.T.); and the Istituto di Anestesia e Rianimazione, Università di Milano, Ospedale S. Gerardo, Monza (A.P., R.F.) — all in Italy. Address reprint requests to Professor Gattinoni at the Istituto di Anestesia e Rianimazione, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy. This study was conducted independently of, but partially funded by, Eli Lilly Italy and Abbott Italy, which supported investigators’ meetings and secretarial activities of the Coordinating Center. *The members of the SvO 2 Collaborative Group are listed in the Appendix. R ECENTLY, increasing attention has been directed to the hemodynamic treatment of critically ill patients, because it has been observed in several studies that patients who survived had values for the cardiac index and oxygen delivery that were higher than those of patients who died and, more important, higher than standard physiologic values. 1-3 Cardiac-index values greater than 4.5 liters per minute per square meter of body-surface area and oxygen-delivery values greater than 650 ml per minute per square meter — derived empirically on the basis of the median values for patients who previously survived critical surgical illness — are commonly referred to as supranormal hemodynamic values. 4 However, there is no agreement about the clinical benefit of a treatment strategy intended to achieve supranormal values, since the few randomized studies available have produced conflicting results. Two studies of surgical patients 5,6 have shown significant decreases in mortality associated with such therapy, whereas studies of patients with sepsis 7 and mixed groups of critically ill patients 8,9 have failed to show significant differences in mortality. In addition, because mixed venous oxygen saturation (SvO 2 ) reflects the balance between oxygen delivery and oxygen consumption 10,11 and because it can be monitored continuously, we thought that targeting therapy to achieve a normal SvO 2 ( 70 percent) could result in a hemodynamic treatment better tailored to the oxygen needs of the patient. We therefore designed a multicenter, randomized trial to determine whether targeting hemodynamic treatment to achieve either supranormal values for the cardiac index or normal values for SvO 2 would improve morbidity and mortality among critically ill patients.