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This supplement aims to provide an update on the latest developments in the use of resuscitation fluids for volume replacement therapy, including an overview of the use of albumin in this and other clinical settings.

Volume replacement can be required in a range of clinical situations and is normally achieved by the use of crystalloids and/or colloids (natural and synthetic). It is generally acknowledged that crystalloids are used for initial treatment for volume replacement. However, in situations where there is a potential for fluid or electrolyte overload, colloids are recommended. Albumin, the only natural colloid, is an effective treatment for volume replacement, and synthetic colloids such as hydroxyethyl starch (HES) and gelatin have also been used in the past. However, recent trials and systematic reviews have shown that the use of HES may lead to serious side effects, including impaired renal function and haemostasis, and that use of gelatin may lead to serious adverse events similar to HES, that is, anaphylactoid reactions, acute kidney injury and bleeding. Two large studies (CHEST and 6S) demonstrated an increased requirement for renal replacement therapy and even mortality (in the 6S trial) in critically-ill patients treated with HES when compared with crystalloids. As a result, medical regulatory bodies in Europe and the US (EMA and FDA, respectively) have deemed that HES should no longer be

given to critically-ill patients or those with sepsis. The FDA also banned the use in cardiac surgery. The CHEST study also showed that the negative effects of HES also extend to non-intensive care surgical patients. In contrast, results from a recent study (CRISTAL) suggest that there are no differences in 28-day mortality rates in patients receiving colloids and crystalloids. However, this does not refute the negative results observed in CHEST, 6S and numerous other studies because weakness in design and conduct of the study makes it a high-risk bias study that does not inform clinical practice. Furthermore, as CRISTAL was an open-label study running over nine years, comparing a mixture of fluids in both the colloids and crystalloid arms, the interpretation of the results is difficult. Albumin, as a natural colloid with significant oncotic properties, appears to be the treatment of choice for volume replacement when colloids are warranted. Also, as a natural protein, albumin has a variety of non-oncotic properties, which may explain some of its beneficial effects beyond volume replacement observed in patients with liver cirrhosis complications (for example, large volume paracentesis due to refractory ascites, spontaneous bacterial peritonitis and hepatorenal syndrome). In addition, albumin has been shown to improve morbidity in intensive care and cardiac surgery.

Uncertainty remains regarding the definite reduction of mortality by albumin

in critically-ill patients as a group , possibly because of clinical trials in highly heterogeneous patient populations. However, administration of albumin was associated with greater intravascular volume expansion and a trend towards reduced mortality in patients with severe sepsis or septic shock, while morbidity studies have demonstrated that albumin treatment leads to reduced morbidity and improvement in organ function in hypoalbuminaemic patients. In addition, albumin has not been shown to have any significant effect on blood coagulation, with the exception of haemodilution. This property, together with its significant volume expanding effect, contributes to the suitability of albumin for volume replacement during or after cardiac surgery. Therefore, it is generally accepted that albumin is the gold standard for volume replacement; however, concerns remain regarding the comparative cost of albumin versus artificial colloids. These concerns are addressed in this supplement where it is evident that, apart from the cost of the resuscitation fluid, other expenses and outcomes (for example, morbidity, mortality, length of intensive care unit stay) should be factored into the final costs. In sum, based on results of recent trials with artificial colloids and albumin, albumin has been demonstrated to be the safest colloid and morbidity and mortality reductions have been established in some patient populations and indications. l


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