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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?

Oliver Hunsicker and Roland C Francis*

Author Affiliations

Department of Anesthesiology and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany

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Critical Care 2012, 16:464  doi:10.1186/cc11836

See related research by Guidet et al.,

The electronic version of this article is the complete one and can be found online at:

Published:15 November 2012

© 2012 BioMed Central Ltd


We argue that assessing the hemodynamic efficacy of hydroxyethyl starch (HES) versus NaCl in patients with severe sepsis requires an algorithm to direct the timing and amount of fluid resuscitation. Such an algorithm may include hemodynamic flow 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 fluid resuscitation in patients with severe sepsis. The target parameters indicating HDS included central venous pressure (CVP) (8 to 12 mm Hg), a poor indicator of fluid 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 fluid 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 defined, 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 differences in mortality, hospital length of stay, or kidney function were found. This study may be showing only that, in the absence of an algorithm to guide fluid resuscitation, intensivists use an unvarying amount of fluids, but it is impossible to know whether these fluids were, in fact, indicated. In patients undergoing major abdominal surgery, hemodynamic algorithms that guide the timing and amount of fluid administration have helped determine the clinical efficacy of fluid therapy [5]. The negative results reported by Guidet and colleagues suggest that hemodynamic algorithms for patients with sepsis are urgently required to accurately compare the hemodynamic efficacy, safety, and outcome of HES versus NaCl fluid replacement.

Author's response

Bertrand Guidet

We thank Hunsicker and Francis for giving us the opportunity to clarify some issues related to fluid replacement and hemodynamic assessment in patients with severe sepsis. When we designed our protocol [1], we used international recommendations that were confirmed 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 (SvO2) to assess whether a patient was a good candidate for fluid 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 (StO2), 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 fluid [1], whereas in the study by Perner and colleagues [10], it was only the ICU clinicians who decided, without further information, to give fluid. In this study, less than half the patients had any measure of CVP or SvO2. This lack of monitoring might have contributed to a higher volume of fluid infused over the first days in comparison with our study and explain the final 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.


CVP: central venous pressure; HDS: hemodynamic stability; HES: hydroxyethyl starch; ICU: intensive care unit; SvO2: venous oxygen saturation.

Competing interests

The authors declare that they have no competing interests.


  1. Guidet B, Martinet O, Boulain T, Philippart F, Poussel JF, Maizel J, Forceville X, Feissel M, Hasselmann M, Heininger A, Van Aken H: Assessment of hemodynamic efficacy and safety of 6% hydroxyethylstarch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study.

    Crit Care 2012, 16:R94. PubMed Abstract | BioMed Central Full Text OpenURL

  2. Marik PE, Baram M, Vahid B: Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares.

    Chest 2008, 134:172-178. PubMed Abstract | Publisher Full Text OpenURL

  3. Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA: Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality.

    Crit Care Med 2011, 39:259-265. PubMed Abstract | Publisher Full Text OpenURL

  4. Perner A, Haase N, Guttormsen AB, Tenhunen J, Klemenzson G, Åneman A, Madsen KR, Møller MH, Elkjær JM, Poulsen LM, Bendtsen A, Winding R, Steensen M, Berezowicz P, Søe-Jensen P, Bestle M, Strand K, Wiis J, White JO, Thornberg KJ, Quist L, Nielsen J, Andersen LH, Holst LB, Thormar K, Kjældgaard AL, Fabritius ML, Mondrup F, Pott FC, Møller TP, et al.: Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis.

    N Engl J Med 2012, 367:124-134. PubMed Abstract | Publisher Full Text OpenURL

  5. Noblett SE, Snowden CP, Shenton BK, Horgan AF: Randomized clinical trial assessing the effect of Doppler-optimized fluid management on outcome after elective colorectal resection.

    Br J Surg 2006, 93:1069-1076. PubMed Abstract | Publisher Full Text OpenURL

  6. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL, International Surviving Sepsis Campaign Guidelines Committee; American Association of Critical-Care Nurses; American College of Chest Physicians; American College of Emergency Physicians; Canadian Critical Care Society; European Society of Clinical Microbiology and Infectious Diseases, et al.: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.

    Crit Care Med 2008, 36:296-327.

    Erratum in Crit Care Med 2008, 36 1394-1396

    PubMed Abstract | Publisher Full Text OpenURL

  7. Ait-Oufella H, Maury E, Lehoux S, Guidet B, Offenstadt G: The endothelium: physiological functions and role in microcirculatory failure during severe sepsis.

    Intensive Care Med 2010, 36:1286-1293. PubMed Abstract | Publisher Full Text OpenURL

  8. Ait-Oufella H, Lemoinne S, Boelle PY, Galbois A, Baudel JL, Lemant J, Guidet B, Maury E, Offenstadt G: Mottling score predicts survival in shock patients.

    Intensive Care Med 2011, 37:801-807. PubMed Abstract | Publisher Full Text OpenURL

  9. Ait-Oufella H, Joffre J, Boelle PY, Galbois A, Bourcier S, Baudel JL, Margetis D, Alves M, Offenstadt G, Guidet B, Maury E: Knee area tissue oxygen saturation is predictive of 14-day mortality in septic shock.

    Intensive Care Med 2012, 38:976-983. PubMed Abstract | Publisher Full Text OpenURL

  10. Perner A, Haase N, Wetterslev J: The authors reply.

    N Engl J Med 2012, 367:1267. PubMed Abstract | Publisher Full Text OpenURL