in a recent issue of critical care , brandt and coworkers   performed fluid resuscitation on pigs with endotoxemia or fecal peritonitis using either moderate volumes of crystalloids ( 103 ml / kg / h ) or larger volumes of crystalloids supplemented by 130/0.4 hydroxyethyl starch ( combined 203 ml / kg / h ) . these protocols were designed to mimic the relative ' restrictive ' and ' liberal ' fluid resuscitation policies that have been previously compared in human major surgery and acute lung injury / acute respiratory distress syndrome [ 2 - 4 ] . in both sepsis models ,
mortality increased with ' liberal ' fluid loading protocols in spite of better haemodynamic stabilization .
although supplemental hydroxyethyl starch use in both study arms was partially ' goal - directed ' - on the basis of cardiac output responses assessed by esophageal doppler - the doses used for fluid loading were relatively fixed rather than completely based on cardiac fluid responses ( fluid responsiveness ) .
the latter is preferable at the bedside , even if we do not formally know whether such therapy causes less morbidity and mortality in septic shock than using fixed volumes or guiding infusion according to relatively crude hemodynamics , such as the central venous pressure , as currently recommended .
it is likely , however , that tailored ' liberal ' therapy decreases the risk for iatrogenic and detrimental fluid overload compared to fixed ' liberal ' therapy [ 6 - 8 ] .
the debate about fixed ' restrictive ' versus ' liberal ' versus ' goal - directed ' therapy in the case of major surgery is also unresolved .
differing results among studies , which may relate to differing case mixes , definitions , hemo - dynamic monitoring techniques / endpoints and treatment strategies , preclude unequivocal conclusions .
the authors used different types of fluid in the ' restrictive ' and ' liberal ' arms , with hydroxyethyl starch used particularly in the latter .
a toxic effect of hydroxyethyl starch can not thus be ruled out , so it is possible that the higher mortality in the ' liberal ' arm was caused , in part , by toxicity rather than large volumes . indeed ,
mortality in the control non - septic pigs receiving the ' liberal ' protocol was 13% ( 1 out of 8) .
toxicity may include renal damage , as was particularly noted from the histology of the ' liberal ' endotoxin - challenged animals . in any case , the histology of several tissues suggested that overhydration and ( pulmonary ) edema had not increased in the ' liberal ' compared to the ' restrictive ' fluid loading groups , even in the presence of so - called colloid plaques observed in lungs , for instance , although the nature of these remains relatively unclear . finally , starch preparations may have multiple anti - inflammatory effects , but we do not know whether this is good or bad during sepsis . collectively , the experiments reported raise the interesting idea that too much of a good thing is detrimental , whether related to relative overtreatment or to toxicity of the hydroxyethyl starch colloid .
a comparison of these experimental results with the literature is difficult because of , for example , highly varying study goals and endpoints .
morisaki and colleagues   found that starches ( more so than ringers lactate ) ameliorated progression of microvascular and parenchymal injury during the development of peritonitis in sheep .
su and colleagues   noted that starch , albumin , gelatin and ringers lactate fluid resuscitation afforded similar survival benefits during protracted fecal peritonitis in sheep , in spite of greater hemodynamic effects with the first two .
this illustrates that the current data provided by brandt and colleagues   may need to be confirmed .
the observations that hemodynamic and mortality endpoints may not go in the same direction also deserve further explanation .
what are the clinical implications of these experimental results ? the potential but unconfirmed ( renal ) toxicity of hydroxyethyl starch is indeed a subject of ongoing research in human septic shock and the current experimental observations may further fuel these efforts [ 13 - 15 ] .
for instance , the potential renal toxicity of starch preparations may depend on volume , type , substitution of starch and the underlying condition of patients in whom fluids are infused , so that general conclusions are hard to draw at this stage [ 13 - 15 ] . that colloids have greater hemodynamic effects , for a given fluid infusion volume , than crystalloids , even in sepsis with increased permeability and potential leakage of the compounds , is corroborated by recent clinical observations .
the outcome benefits and drawbacks of fluid resuscitation in sepsis and shock may not solely relate to hemodynamic effects , so that more is not always better , even if overt overhydration and ( pulmonary ) edema do not occur .
the experimental findings remind us that outcome may also be a matter of the type of fluid used for initial resuscitation during septic shock
. obviously , this relates , among other factors , to the increasing evidence that starch solutions have important side effects , particularly when exceeding recommended maximum daily doses .
 in a recent issue of critical care , brandt and colleagues report the effects of a ' liberal ' fluid loading protocol compared to a more ' restrictive ' protocol on hemodynamics and mortality in pigs in which septic shock had been induced . 
 it appears that the former protocol was associated with higher mortality in spite of improved hemodynamics compared to the latter . 
 the results of the paper are discussed here in view of the scope and mechanisms of these findings . with regard to fluid resuscitation 
 , they indicate that too much of an otherwise good thing is harmful , even if overhydration and edema formation seem to have been prevented . 
 they also do not exclude a specific toxic effect of the larger volumes of hydroxyethyl starch in the ' liberal ' strategy . 
 the precise nature of a toxic effect remains obscure , however , but may involve the kidneys . 
Introduction
Volume and type of fluid in the resuscitation from sepsis
Clinical implications
Conclusion
Competing interests