The International Sepsis Forum's frontiers in sepsis: high cardiac output should be maintained in severe sepsis
© BioMed Central Ltd 2003
Published: 4 July 2003
Despite a usually normal or high cardiac output, severe sepsis is associated with inadequate tissue oxygenation, leading to organ failure and death. Some authors have suggested that raising cardiac output and oxygen delivery to predetermined supranormal values may be associated with improved survival. While this may be of benefit in certain patients, bringing all patients to similar, supranormal values, is simplistic. It is much preferable to titrate therapy according to the needs of each individual patient. A combination of variables should be used for this purpose, in addition to a careful clinical evaluation, including not only cardiac output but also the mixed venous oxygen saturation and the blood lactate concentrations. The concept is to assess the adequacy of the cardiac output in patients with severe sepsis, enabling management strategies aimed at optimizing cardiac output to be tailored to the individual patient.
Keywordsmixed venous oxygen oxygen delivery oxygen uptake saturation
The 'supranormal' studies
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  and Gattinoni and coworkers  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 lies in identifying those patients.
Should we maintain adequate cardiac output in all patients with septic shock?
The available studies suggest that rather than protocolize all patients to increased cardiac output and DO2, this strategy should be tailored to the individual patient. Hayes and coworkers  suggested that survivors from septic shock are characterized by an ability to increase DO2 and VO2, whereas nonsurvivors do not have sufficient physiologic reserve to do this, and in such patients excessive doses of vasopressors or fluids worsen an already bad situation. Rather than making attempts to target cardiac output and DO2 randomly in all patients, our approach should rather be to try to restore hemodynamic stability, which will necessitate different approaches in different patients. Indeed, no one would dispute the need for clinical interventions to enhance DO2 and support the circulation where tissue perfusion is clearly inadequate. The problem lies in identifying those patients in whom tissue hypoxia is less overt, who may in fact have 'normal' hemodynamic parameters, and augmenting DO2 in such patients may necessitate reaching 'supranormal' values.
Importantly, it is not necessary to calculate DO2. Moreover, the relationship between VO2 and DO2 is subject to mathematical coupling of data. In complex cases, the relation between cardiac index and oxygen extraction ratio may be helpful, especially in anemia [15, 16]. Finally, blood lactate levels may help to identify the patient who requires a higher cardiac output because survivors from septic shock have significantly lower initial blood lactate levels and their blood lactate levels are raised for shorter periods of time .
Another important feature may be the timing of optimization. In the early studies conducted by Shoemaker and coworkers  that showed improved outcome in surgical patients, optimization was commenced before the surgical procedure. Rivers and coworkers  recently showed the beneficial effects of early goal-directed therapy, within 6 hours of diagnosis of septic shock, over standard therapy. The methods for increasing cardiac output or DO2 (e.g. fluids, inotropes, and blood transfusions) may also impact on results.
DO2 = oxygen delivery
SvO2 = mixed venous oxygen saturation
VO2 = oxygen consumption.
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