of critically ill patients , or during a specific phase of their treatment . Additionally , in the absence of a detrimental effect , the Surviving Sepsis Campaign guidelines for the management of severe sepsis and septic shock have recommended ( graded as grade 2C ) to use albumin during the first phase of fluid resuscitation , especially when large amounts of crystalloids are required . 22
Well-designed RCTs are needed as a basis for a better assessment and understanding of factors which can improve the beneficial effects of albumin . These factors include but are not limited to patient characteristics ( severe sepsis versus septic shock ), timing of treatment ( early versus late ), trigger for albumin administration ( volume versus albumin replacement ), and concentration of albumin solutions ( 20 % versus 4 – 5 %). In this regard , results of two ongoing trials in patients with septic shock , the ALBIOSS-BALANCED – Albumin Italian Outcome Septic Shock trial ( NCT03654001 ) and the Albumin Replacement Therapy in Septic Shock ( ARISS ) trial ( NCT03869385 ) – are awaited .
Clinical evidence of secondary functions Historically , the evidence investigating the clinical benefits of the secondary functions of human albumin has been relatively scarce . In relation to the antioxidant properties of albumin , one study in patients with acute lung injury reported increased plasma thiol levels after albumin supplementation , 23 suggesting that albumin replacement improved overall plasma antioxidant capability . Other work has found that infusion of albumin to critically ill , hypoalbuminemic patients appeared to be associated with a reduction of the severity and the number of organ failures , indirectly suggesting a clinical benefit related to secondary functions of albumin . 24 Del Giudice and colleagues 25 also demonstrated in a series of in vitro experiments , that albumin appeared to be highly resistant to hypochlorite oxidation , illustrating the powerful biological buffering capacity of albumin .
Liver disease , in particular cirrhosis , is an immune compromised state , with innate immune system defects . 26 In a multi-model investigation , 27 high levels of the cyclooxygenase-derived eicosanoid prostaglandin E2 ( PGE2 ) were found in patients with acute decompensation of cirrhosis . The use of albumin appeared to modulate PGE2-mediated immune dysfunction by reducing circulating PGE2 levels , thereby significantly improving the plasma-induced impairment of macrophage proinflammatory actions . Furthermore , in a review of studies , the long-term use of albumin infusion appeared to improve the clinical outcomes in decompensated cirrhosis patients . 28
Finally , it is conceivable that albumin administration can be used to counteract infections . Giacobbe et al 29 reported that the presence of hypoalbuminemia was a strong predictor for acute kidney injury during treatment with the antibiotic colistin . The authors hypothesized that due to a high degree of binding between colistin and albumin , it was possible that albumin possibly minimized AKI .
Conclusion There is a strong biologically plausible rationale for using human albumin in the critically ill patient , despite the limited clinical evidence which is compounded to some extent by the heterogeneity of the critically ill population . Future studies will therefore need to focus on specific cohorts to more clearly define the benefits from using albumin in the critically ill .
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