colloid solutions . 14 Nevertheless , these findings do not reject the hypothesis that the oncotic properties of human albumin may have beneficial effects in specific categories of critically ill patients , or specific phase of their treatment , especially regarding the fluid therapy applied . In a post hoc analysis performed on patients with severe sepsis included in the SAFE trial , the use of 4 % albumin solution was associated with an increased central venous pressure and a reduced heart rate over the first seven days as compared with crystalloids , suggesting a greater intravascular blood volume . 15 Similar findings were also observed in the ALBIOS trial , which randomised patients with severe sepsis or septic shock to receive 20 % albumin in addition to crystalloids or only crystalloids for fluid replacement during the first 28 days of treatment . 16 Patients receiving albumin and crystalloids did show a higher mean arterial pressure and a lower daily net positive fluid balance over the first seven days of treatment , as compared with those receiving just crystalloids .
Very likely , this is the reason why , in the absence of a detrimental effect , the Surviving Sepsis Campaign guidelines for the management of severe sepsis and septic shock have included the suggestion ( graded as grade 2C ) of using albumin during the first phase of fluid resuscitation , especially when large amounts of crystalloids are required . 17 In a meta-analysis including more than 27,000 critically ill patients and investigating the possible effects of different type of colloids ( including albumin ) on haemodynamics , as compared to the use of crystalloids , the use of albumin appeared to be associated with a higher mean arterial and central venous pressure , and more adequate cardiac index . 18
Clinical evidence : secondary functions Historically , the current evidence investigating the clinical benefits of the secondary functions of human albumin has been relatively scarce until the last decade . Certainly , the molecular specificity and complexity of some of these properties make this task difficult . Nonetheless , indirect evidence , paralleled by preliminary findings ( both experimental and clinical ), may provide new insights . Moreover , in the last years , specific aspects on the possible albumin ancillary properties have been investigated quite properly , leading to novel findings related to specific aspects .
On the antioxidant properties of human albumin , two different studies , one in patients with severe sepsis 19 and the other in patients with acute lung injury , 20 have reported increased plasma thiol levels after albumin supplementation . Moreover , such supplementation appeared to improve thiol-dependent antioxidant properties of plasma obtained from these categories of patients , suggesting a direct effect of albumin replacement on the overall plasma antioxidant capability . In addition , in a single-centre study including critically ill patients with hypoalbuminaemia , albumin supplementation for a maximal period of 28 days appeared to be associated with a reduction of the severity and the number of organ failures , indirectly suggesting a clinical benefit related to albumin secondary properties . 21
More recently , O ’ Brien et al , in a multimodel investigation , elucidated the possible role of albumin , during cirrhosis , on the immunosuppressive effects of cyclooxygenasederived eicosanoid prostaglandin E2 ( PGE2 ). 9 In this context , albumin administration appeared to actively reduce circulating PGE2 levels , thereby significantly improving the plasma-induced
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