The International Sepsis Forum's frontiers in sepsis: high cardiac output should be maintained in severe sepsis

Sepsis is associated with systemic, mediator-induced alterations in oxygen utilization, including increased oxygen demand, altered oxygen extraction, and decreased myocardial contractility (Fig. 1). Hence, despite a normal or high cardiac output, severe sepsis and septic shock are characterized by an inadequate organ oxygenation, leading ultimately to multiple organ failure and death. Almost 20 years ago, Abraham and colleagues [1] noted that survivors from septic shock had significantly higher cardiac indexes prior to the shock episode than did nonsurvivors, leading to the suggestion that pushing patients to reach high and even 'supranormal' levels of cardiac output could be beneficial. This early hypothesis has fueled an ongoing debate regarding the potential benefit or harm of this strategy in the patient with septic shock.Several groups have indicated increased survival in various groups of patients treated with a strategy to increase cardiac output or oxygen delivery (DO2) to so-called 'supranormal' values (cardiac index ≥ 4.5 l/min per m2, DO2 < 600 ml/min per m2 and oxygen consumption [VO2] >170 ml/min per m2) [2-9]. However, two notable studies conducted in mixed groups of critically ill patients by Hayes and coworkers [10] and Gattinoni and coworkers [11] showed that supranormal DO2 values do not result in improved outcomes. A possible explanation for those findings is that, unlike many of the other studies in this field, the heterogeneity of the critically ill patients included in the studies influenced the results. Thus, although some individuals might well have benefited from the trial strategy, these positive results may have been negated by harmful effects in other patients who perhaps had already been adequately resuscitated and therefore received excessive doses of vasopressor agents or fluids. There is little doubt that, in certain patients, achieving and maintaining high levels of cardiac output is associated with improved outcomes; the difficulty