a septic patient is in your intensive care unit and you are concerned that he is behind on his intravascular volume . for a variety of reasons you have decided you would like to give him intravenous colloids .
frdrique schortgen and laurent brochard capillary leakage during sepsis is a reason for recommending the use of macromolecules that could preserve the colloid osmotic pressure ( cop ) .
the high cost of albumin has facilitated the widespread use of hydroxyethylstarches ( he s ) .
outcome studies on sepsis are scarce , and the reasons why we should use he s remain speculative or based on short - term physiological data .
we will briefly describe how uncertain are the clinical benefits of these products and , by contrast , how strong is the evidence for numerous adverse effects .
both crystalloids and colloids have a similar ability to achieve sufficient volume loading when the volume administered takes into account the capacity of the solution to remain in the intravascular space . to achieve an equivalent plasma volume expansion ,
a fourfold greater volume of crystalloid may be needed in comparison with 5% albumin . maintaining cop by administration of he
one study including septic patients found a higher incidence of pulmonary oedema after crystalloids than after he s .
most clinical results have been disappointing , however , and a meta - analysis showed that pulmonary oedema occurrence is similar with colloids or crystalloids . indeed , in the context of a free course of macromolecules across a damaged alveolocapillary membrane , the starling equation indicates that colloidal forces can no longer stop fluid shift .
an attractive , although unproven , pharmacological effect of he s comes from experimental studies suggesting that he s could improve microcirculation .
boldt and colleagues found a better intramucosal ph in patients receiving he s in comparison with albumin , but two recent studies in septic hypovolaemic patients showed that he s did not improve splanchnic circulation whereas gelatins did .
the case for adverse events secondary to administration of he s is much stronger and concerns coagulation disorders , acute renal failure , liver failure and pruritis [ 8 - 12 ] . initially shown in a situation of ischaemia reperfusion ( i.e. renal transplant recipients )
, the nephrotoxicity of hydroxyethylstarch has been demonstrated in a randomised study during severe sepsis . in comparison with gelatins , he s 200 kda/0.6 induced a twofold higher incidence of acute renal failure .
the adverse effects of he s may depend on the molecular weight and the degree of substitution ( proportion of hydroxylethyl groups on glucose molecules ) .
the conflicting results coming from coagulation studies cast doubts whether an optimal combination for these two parameters has yet been found . comparing he s 200 kda/0.5 and 130 kda/0.4 , jamnicki and colleagues found the same disturbances in in vitro coagulation tests .
a recent meta - analysis in cardiac surgical patients showed that postoperative bleeding was more frequent with he s , whatever the molecular weight , than with albumin .
concerning acute renal failure , no comparative study supports the hypothesis that the newer compounds are safer . in a prospective randomised study including 150 postoperative patients with sepsis , a 50% increase in the serum creatinine was found at day 3 in the hydroxyethylstarch 200 kda/0.5 group against only a 6% increase with albumin .
this difference was not significant , but this result again suggests that doing no harm should be our primary goal . if the only colloids available are he s , the actual equipoise regarding efficacy means that we choose crystalloids to avoid adverse effects on organ function .
ellen burnham and greg s martin fluid exchange across the capillary endothelium obeys starling 's law { v = kf [ ( pc - pi ) - (c - i ) ] } , which describes the forces governing fluid flux across a semipermeable membrane , such as the human vasculature .
hydrostatic pressure and cop (  ) are the primary determinants of fluid flux in this system . when these forces are in balance , homeostasis between the intravascular and extravascular fluid compartments is maintained .
the difference in hydrostatic pressure ( pcapillaries - pinterstitium ) pushes fluid out of the vasculature , while the difference in cop ( capillaries - interstitium ) draws fluid into the vasculature .
the relative effect of oncotic pressure is modulated by the reflection coefficient (  ) , describing the integrity of the capillary wall in preventing translocation of proteins .
colloids were developed as a durable alternative to crystalloids and blood products for patients requiring fluid resuscitation .
, this translates into albumin versus starches , gelatins , dextrans or combination solutions . because of cost differentials , conflicting evidence and the underemphasis of cop in shock states , the solution of choice for resuscitating patients is controversial .
the utilisation of a crystalloid solution in volume resuscitation , especially in situations where patients are hypoproteinemic , such as sepsis , may promote extravasation of volume out of the vascular space and into the interstitium , where it is of little help in rectifying hypotension .
physiologically , the use of resuscitative fluid containing osmotically active molecules of low molecular weight that are biodegradable with a moderate halflife would be ideal in septic patients , who have greater capillary permeability and , frequently , a low cop .
he s solutions contain molecules with a wide range of molecular weights and have an effect on intravascular volume lasting about 24 hours . in the intravascular compartment
, he s are progressively hydrolysed into smaller fractions that are ultimately excreted by the kidneys .
colloidal agents are more efficacious at restoring plasma volume compared with crystalloids , per unit of fluid given .
furthermore , he s continue to provide volume expansion even in states of capillary permeability .
investigators have demonstrated that , in hypovolaemic shock , resuscitation with starches or albumin results in a lower incidence of pulmonary oedema , compared with crystalloids . additionally , maintenance of cop may prevent complications of critical illness , including refractory acidosis , acute respiratory distress syndrome , prolonged mechanical ventilation and mortality associated with crystalloid resuscitation .
apart from being pure volume expanders , he s have specific pharmacologic properties that may be beneficial in sepsis , such as lowering the circulating levels of adhesion molecules , and thus potentially reducing endothelial activation and damage . in septic patients , endogenous vasopressor production is decreased in patients receiving he s compared with other colloids . additionally , he s may exert useful effects on the microvascular coagulation cascade of these patients by elevating levels of protein c and protein s .
the use of he s as a resuscitative fluid in this patient with septic shock makes sound physiologic sense , particularly if cop is already reduced .
experimental data have demonstrated the efficacy of he s in the restoration of intravascular volume , and the unique pharmacologic properties of he s may provide additional benefit . finally ,
frdrique schortgen and laurent brochard in the absence of abnormally high hydrostatic pressure , low cop does not promote lung fluid accumulation . whereas a low cop may induce soft tissue oedema , several effective mechanisms protect against alveolar flooding .
low cop is rather a marker of severity for capillary leakage and of the amount of volume needed before acute respiratory distress syndrome onset .
the ability of plasma expanders to reverse microvascular damages is not limited to starches , or even to colloids .
one might not forget that the best way to reverse low cop and microvascular damages in sepsis remains early and adequate anti - infectious treatment .
ellen burnham and greg s martin for improving outcomes in critically ill patients with severe sepsis there is an absence of evidence regarding intravenous solutions .
colloids have physiologic advantages over crystalloids , but suffer from higher acquisition costs . in light of recent evidence specifically regarding he s , advocating their use in patients with severe sepsis
although he s may be the economic colloids of choice , we must focus our prescribing choices on patient - centred outcomes .
association does not indicate causation and , until clinical trials evaluating appropriate clinical outcomes are performed , we will continue to deliver imprecise critical care .
intensivists should prescribe intravenous therapy based upon patient - specific factors , recognising that newer starches might obviate the associated risks , which are also absent with natural colloids .
 there are few issues in critical care medicine that have a less clearly defined standard of care than the intravenous fluid choice for resuscitation . 
 natural colloids ( such as albumin ) became popular during the second world war when there was a need to develop a portable , easily stored , blood substitute . 
 early successes led to widespread use and a multibillion dollar industry . 
 it is not surprising given the large demand , high costs and potential adverse effects of natural colloids that synthetic colloids have emerged . in the present article , two groups of clinical investigators remind us of the controversies surrounding the use of synthetic colloids . 
The scenario
Pro: Yes, hydroxyethylstarches should be avoided in septic patients
Con: No, hydroxyethylstarches should not be avoided in septic patients
Pro's response
Con's response
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