Supranormal cardiac index or normal mixed venous oxygen saturation values did not improve morbidity or mortality in critical care
ACP J Club. 1996 May-June;124:72. doi:10.7326/ACPJC-1996-124-3-072
Gattinoni L, Brazzi L, Pelosi P, et al for the SvO2 Collaborative Group. A trial of goal-oriented hemodynamic therapy in critically ill patients. N Engl J Med. 1995 Oct 19;333:1025-32.
To determine whether using hemodynamic therapy to achieve supranormal levels for the cardiac index or normal levels for the mixed venous oxygen saturation (SvO2) improves morbidity and mortality in critically ill patients.
Randomized controlled trial with 6-month follow-up.
56 intensive care units (ICUs) in Italy.
762 patients (mean age 61 y) who were admitted to the participating ICUs and had a simplified acute physiology score ≥ 11 and 1 of the following: considered to be high risk after surgery, massive blood loss, septic shock or sepsis syndrome, acute respiratory failure, or multiple trauma. Follow-up was complete for 95%.
All patients received at least 5 days of hemodynamic therapy consisting of volume expansion inotropic agents, vasodilators, and vasopressor agents. Patients were allocated to 3 different hemodynamic goals: a normal cardiac index (2.5 to 3.5 L of blood/min per m2 of body surface area) (control group, n = 252); a supranormal cardiac index (≥ 4.5 L/min per m2 of body surface area) (cardiac-index group, n = 253); or a normal SvO2 (≥ 70%) or difference of < 20% between the arterial oxygen saturation and the SvO2 (oxygen-saturation group, n = 257).
Main Outcome Measures
Mortality at ICU discharge and at 6 months and morbidity estimated by the number of dysfunctional organ systems.
Analysis was by intention to treat. Target hemodynamic values were reached by 94.3% of patients in the control group, 44.9% of patients in the cardiac-index group, and 66.7% of patients in the oxygen-saturation group (P for both treatment groups compared with the control group < 0.001). Patients in the control group, cardiac-index group, and oxygen-saturation group did not differ for mortality at ICU discharge (48.4%, 48.6%, and 52.1%, respectively; P = 0.64) or for mortality at 6 months (62.3%, 61.7%, and 63.8%, respectively; P = 0.88). At completion of 5 days of treatment, the groups did not differ for number of dysfunctional organs (P = 0.66). Patients in the control group, the cardiac-index group, and the oxygen-saturation group had similar lengths of stay in the ICU (26, 22, and 24 d, respectively; P = 0.5).
Hemodynamic therapy to achieve supranormal cardiac index levels or normal mixed venous oxygen saturation levels did not affect morbidity or mortality in critically ill patients. Achieving a supranormal cardiac index level was more difficult than achieving normal levels for the cardiac index or for the mixed venous oxygen saturation.
Sources of funding: In part, Eli Lilly Italy and Abbott Italy.
For article reprint: Professor L. Gattinoni, Istituto di Anestesia e Rianimazione, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy. FAX 39-2-5830-3831.
Several studies, most of which are plagued with methodologic problems in both design and analysis, have suggested that therapy aimed at achieving supranormal values of hemodynamic variables, whether before surgery or after any injury or acute illness, could improve the outcome of critically ill patients. The large, randomized, multicenter, 3-arm trial by Gattinoni and colleagues shows no benefit (either in terms of organ dysfunction or in early or late mortality) of maximizing hemodynamic parameters after admission to the ICU in patients at high risk for organ dysfunction and death. These results were consistent across various subgroups of patients, whether they were enrolled after major surgery, massive blood loss, severe sepsis or septic shock, acute respiratory failure, or multiple trauma. Similar to previous studies, a substantial proportion of patients randomized to supranormal values of cardiac index did not reach the targeted values. The negative results, however, were consistent across patient subgroups that achieved the target goals, whether within the first 24 hours after enrollment or later.
Although unblinded, this study is the second well-designed study to show that no benefit occurs from boosting the cardiac index in high-risk, critically ill patients after their admission to the ICU. It confirms and expands previous results obtained by Hayes and colleagues (1), who found that using vasoactive drugs in hypotensive patients who were unresponsive to a fluid challenge in an attempt to achieve supranormal values of cardiac index and oxygen delivery actually increased mortality.
The existing evidence suggests that, in various categories of critically ill patients, maximizing hemodynamic parameters to achieve supranormal values after ICU admission is at best ineffective and could be potentially harmful. The question that remains is whether initiating this intervention before surgery has any benefit in high-risk patients.
Christian Brun-Buisson, MD
Hôpital Henri MondorCréteil, France