Assessment of hemodynamic efficacy and safety of 6% hydroxyethyl starch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: how to guide fluid therapy?

We argue that assessing the hemodynamic effi cacy of hydroxyethyl starch (HES) versus NaCl in patients with severe sepsis requires an algorithm to direct the timing and amount of fl uid resuscitation. Such an algorithm may include hemodynamic fl ow parameters. In a recent issue of Critical Care, Guidet and colleagues [1] reported that a smaller amount of 6% HES 130/0.4 versus 0.9% NaCl was required to achieve hemodynamic stability (HDS) during the initial phase of fl uid resuscitation in patients with severe sepsis. Th e target parameters indicating HDS included central venous pressure (CVP) (8 to 12 mm Hg), a poor indicator of fl uid responsiveness [2], and a large urine output (>2 mL/kg per hour), and therefore pose a risk of over-infusion. Other authors have reported that over-infusion, elevated CVP, and excessive fl uid resuscitation with HES are associated with increased mortality in patients with sepsis [3,4]. In contrast, after initial HDS was achieved, no such target parameters were defi ned, and so the cumulative volumes of study drug infused over the course of four consecutive days in the intensive care unit (ICU) were similar for the HES (2,615 mL) and NaCl (2,788 mL) groups. No diff erences in mortality, hospital length of stay, or kidney function were found. Th is study may be showing only that, in the absence of an algorithm to guide fl uid resuscitation, intensivists use an unvarying amount of fl uids, but it is impossible to know whether these fl uids were, in fact, indicated. In patients undergoing major abdominal surgery, hemodynamic algorithms that guide the timing and amount of fl uid administration have helped determine the clinical effi cacy of fl uid therapy [5]. Th e negative results reported by Guidet and colleagues suggest that hemodynamic algorithms for patients with sepsis are urgently required to accurately compare the hemodynamic effi cacy, safety, and outcome of HES versus NaCl fl uid replacement.

We argue that assessing the hemodynamic effi cacy of hydroxyethyl starch (HES) versus NaCl in patients with severe sepsis requires an algorithm to direct the timing and amount of fl uid resuscitation. Such an algorithm may include hemodynamic fl ow parameters.
In a recent issue of Critical Care, Guidet and colleagues [1] reported that a smaller amount of 6% HES 130/0.4 versus 0.9% NaCl was required to achieve hemodynamic stability (HDS) during the initial phase of fl uid resuscitation in patients with severe sepsis. Th e target parameters indicating HDS included central venous pressure (CVP) (8 to 12 mm Hg), a poor indicator of fl uid responsiveness [2], and a large urine output (>2 mL/kg per hour), and therefore pose a risk of over-infusion. Other authors have reported that over-infusion, elevated CVP, and excessive fl uid resuscitation with HES are associated with increased mortality in patients with sepsis [3,4].
In contrast, after initial HDS was achieved, no such target parameters were defi ned, and so the cumulative volumes of study drug infused over the course of four consecutive days in the intensive care unit (ICU) were similar for the HES (2,615 mL) and NaCl (2,788 mL) groups. No diff erences in mortality, hospital length of stay, or kidney function were found. Th is study may be showing only that, in the absence of an algorithm to guide fl uid resuscitation, intensivists use an unvarying amount of fl uids, but it is impossible to know whether these fl uids were, in fact, indicated. In patients undergoing major abdominal surgery, hemodynamic algorithms that guide the timing and amount of fl uid administration have helped determine the clinical effi cacy of fl uid therapy [5]. Th e negative results reported by Guidet and colleagues suggest that hemodynamic algorithms for patients with sepsis are urgently required to accurately compare the hemodynamic effi cacy, safety, and outcome of HES versus NaCl fl uid replacement.

Bertrand Guidet
We thank Hunsicker and Francis for giving us the opportunity to clarify some issues related to fl uid replacement and hemodynamic assessment in patients with severe sepsis. When we designed our protocol [1], we used international recommendations that were confi rmed by the revision of the Surviving Sepsis Campaign [6]. Given the multicenter nature of the trial, in which more than 20 ICUs participated, it was impossible to standardize an algorithm that was agreed upon by everybody and feasible 24 hours a day in all ICUs. However, all centers used tools in addition to CVP, urine output, and venous oxygen saturation (SvO 2 ) to assess whether a patient was a good candidate for fl uid loading.
As a matter of fact, considering the endothelial dysfunction induced by sepsis [7], we strongly advocate the use not only of macrocirculatory parameters (mean arterial pressure and cardiac output) but also of microcirculatory parameters such as mottling score and knee tissue oxygen saturation (StO 2 ), as we have shown in previous studies that there may be a discrepancy between macro-and microcirculation after initial resuscitation [8,9].
In our study, the baseline values suggested that patients should receive fl uid [1], whereas in the study by Perner and colleagues [10], it was only the ICU clinicians who decided, without further information, to give fl uid. In this study, less than half the patients had any measure of CVP or SvO 2 . Th is lack of monitoring might have contributed to a higher volume of fl uid infused over the fi rst days in comparison with our study and explain the fi nal results on renal function and mortality. In conclusion, I do agree that an integrative approach should be advocated in order to avoid over-infusion but also under-resuscitation, in particular in the early hours after onset of severe sepsis or septic shock.