Taken together, this strategy of fluid therapy may be associated with an increased risk of fluid overloading that may have contributed to the observed higher rate of patients getting RRT and mortality, at least in part [3].Moreover, banishing selleck chemical Erlotinib colloids from clinical routine and preferentially using non-colloids might likely result in higher amounts of crystalloids, albumin and red blood cells needed to reach haemodynamic endpoints. This new paradigm might open the ‘floodgates’ for the use of even more amounts of crystalloid fluids potentially increasing the incidence of fluid overload and interstitial oedema. Recent observational studies [26-28] suggested that positive fluid balance is associated with increased morbidity and mortality.

Obviously sicker patients who never reverse their capillary permeability deficit have a positive fluid balance leading to an increased risk of mortality. Nevertheless, using multivariate analysis, positive fluid balance remained an independent risk factor for 28-day mortality after adjustment for age, gender, diabetes, hypertension, diuretic use, non-renal sequential organ failure assessment (SOFA) and sepsis [26]. That is why the results of these studies should be critically re-evaluated, and why any planned prospective RCTs in the field of volume resuscitation in critically ill patient should adequately consider the suggestions outlined in this paper.General limitations of the included trialsWe are concerned that major limitations may have biased previous study results, and that they are not adequately considered within the ongoing discussion.

In this respect, we would like to highlight a few very important issues:1. Fluid therapy before inclusion of patientsUp to 52% [3] and 59% [1] of all study patients had already received large amounts of colloids for acute haemodynamic stabilisation before formal randomisation. In this respect, a substantiate characterisation of HES-specific effects is very difficult, and late randomisation of patients may lead to inclusion of patients who have well exceeded predefined haemodynamic targets. It makes the whole story even more critical as those studies recommending not using colloids in general in the ICU had stabilised their patients with colloids initially before randomisation [1-3].2. Prolonged administration of HESIn some studies, HES was allowed to be administered up to a maximum of 90 days [6,7].

However, prolonged administration of Batimastat HES after the initial phase of haemodynamic instability increases the risk of giving HES to non-hypovolaemic patients [5-7,13,17]. Thus, persistent use with presumably weak indication has no beneficial effect or may even be harmful.3. No control of other risk factors for mortality/renal failure (for example, blood transfusion)More patients in the starch groups received packed red cells, although the transfusion algorithm was not standardised.