Hartog et al.1 aimed to review the rationale for indication to use colloids for fluid administration, with a focus on the newly developed hydroxyethyl starch (HES), in comparison with crystalloids. The authors listed the classically mentioned arguments: colloids are more effective plasma expanders than crystalloids; synthetic colloids are as safe as albumin; HES solutions have the best risk/benefit profile among the synthetic colloids; and the third-generation HES 130/0.4 has fewer adverse effects than older starches. The tremendous effort made to screen almost all of the literature, with special attention to randomized clinical trials and meta-analyses, provides a complete overview.
Several concepts or ideas have to be kept in mind for fluid resuscitation, which is the essential method of cardiovascular support in intensive care and anesthesiology. Why is fluid given? The decision to give fluid has several goals, which are more or less associated: (1) to increase the circulatory blood volume, supposed to increase stroke volume and cardiac output with blood pressure increase2; and (2) to compensate for fluid losses or inadequacy between the container (cardiovascular circuit) and the contained volume, as observed in vasodilatation.3 Why is fluid with expanding properties given? Basically, the perfusion of fluid with high oncotic pressure is supposed to better fill the vascular system, adding to the given volume a proportion of volume expanded from extravascular tissue.4,5 As a result, a smaller fluid volume has to be given to achieve adequate vascular fluid replacement. This well-acknowledged concept is supported by physiology, because plasma contains a large amount of proteins, particularly albumin, creating a physiological oncotic pressure of approximately 25 mm Hg. The acute loss of albumin as observed in nephrotic syndrome induces major peripheral edema, confirming the role of oncotic pressure in the maintenance of fluid partition. If this concept is important for acute oncotic pressure changes, it seems less relevant for chronic situations, because familial analbuminemia disease does not induce interstitial edema.6 Among the 39 reported cases of congenital analbuminemia, the tolerance is relatively good, with minor edema and few adverse symptoms.7 Mechanisms to compensate for hypooncotic pressure might occur in acute situations after a duration of 1 or 2 days.
For clinicians, several situations have to be considered: acute fluid challenge versus slower infusion; indication for perioperative hemodynamic optimization versus fluid resuscitation of intensive care patients; artificial versus natural colloids; fluids with high versus moderately elevated oncotic pressure. In an anesthesiology context, fluid optimization is given with proven efficiency, to limit perioperative complications and to reduce hospital length of stay.8 It seems from the literature that, more than the type of fluid, the benefit is in relation to cardiac output increase, without clear mechanistic information. No advantage of one type of fluid over another has been proven, which does not provide motivation for using colloids instead of crystalloids.8 In intensive care unit situations, the indication is more complex, because of the frequent systemic inflammation, with important consequences such as capillary leak syndrome.9 With such abnormal vascular permeability, there is the potential for artificial colloids to leak through the vascular barrier. The interstitial clearance of these products then becomes an important issue for tolerance, even if it is not really well documented. Such a clearance might differ from one type of colloid to another, according to their pharmacological properties. This uncertainty points out the need for caution in use of colloids in acute situations.
The present exhaustive review lists all the potential toxic effects, with special focus on kidney damage.1 The first HES fluids, with high molecular weight and percentage of substitution, were clearly toxic, especially for the kidney, the key organ for filtration processes. Such a situation is typically observed in severe sepsis or septic shock, during which the complex combination of capillary leak and tissue infiltration by immune cells may promote organ failure. Among these, kidney injury was shown to be associated with a high rate of death even after severity adjustment, especially when fluid balance was largely positive.10–12 The risk of adding a factor such as colloids, particularly artificial ones, should perhaps be avoided. As summarized in this review, kidney osmotic nephrosis lesions were shown to be more frequent and major when colloids were given. Randomized controlled trials and meta-analyses confirm this opinion despite criticism of study design, type of colloids, and doses.13 Even if systemic inflammation is limited, such an impact on kidney damage seems more frequent when colloids are given.14 Importantly, the review highlights that all colloids are not equivalent, with differences in complications. Published studies favor the opinion that HES is more capable of inducing renal failure or injury, even though few comparative data with the other colloids have been published.15 Before conclusions can be drawn on this issue, trials should be performed comparing the different colloids, with the precaution to achieve a comparable oncotic pressure. The famous SAFE study comparing albumin with crystalloids, which failed to demonstrate any benefit of colloids, cannot be extrapolated to all types of albumin product.16 A 4% or 5% solution of albumin differs largely from a 20% or 25% albumin solution in terms of oncotic pressure, even if final oncotic pressure is comparable.
In this outstanding review, the rationale for fluid replacement is rigorously clarified. For anesthesia, the recommendation to use crystalloids for fluid loading and hemodynamic optimization more than colloids sounds logical. In the context of acute inflammation, the decision is more debatable. In addition to the expander property and the potential toxicity, other aspects should be considered to evaluate colloids' effectiveness in the future. Even if an expander fluid, i.e., colloid, appears reasonable, the negative benefit/risk ratio calls their use into question. The clearly demonstrated higher incidence of renal injury in septic patients, with no clear differences between the various artificial colloids, strongly supports the decision to limit these products in this syndrome. However, this incidence was not demonstrated in critically ill patients.17 Finally, that the recent HES products have a good safety index remains to be demonstrated. Other issues might be relevant and are for the moment poorly documented. For the role of colloids on microcirculation, data are needed to draw definitive conclusions. Concerning the optimal fluid therapy and improvement in microcirculatory perfusion, data are not yet available.18 Because administered fluid will surround cells and, particularly, immune cells, significant data must be generated on the modification of inflammatory patterns in relation to the type of fluid used. Few clinical data have been published showing the absence or presence of inflammatory phenotype modifications induced by crystalloids or colloids. The impact on physico-chemical properties of plasma and extravascular fluid induced by fluid resuscitation has received little attention and should be detailed. All of these unanswered questions allow us to draw only cautious conclusions.
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