impairment of macrophage pro-inflammatory actions . Thus , albumin-containing solutions were effective in attenuating PGE2-mediated immunosuppression , and the consequent risk of secondary infections , especially in patients with acutely-decompensated cirrhosis .
Further studies have recently provided also new insights on the potential efficacy of albumin administration as a beneficial ‘ tool ’ to counteract infections . Del Giudice and colleagues elucidated , in a series of in vitro experiments , the effects of the exposition to hypoclorite species on the molecular structure of human albumin . 22 Albumin appeared to be a molecule highly resistant to hypochlorite oxidation . At the same time , the link of hypochlorite to albumin as chloramines , appeared to be an effective way by which albumin might transfer local bactericidal activity systemically . In addition , Giacobbe et al nicely observed that hypoalbuminaemia is a strong predictor of risk for acute kidney injury during treatment with the antibiotic colistin , providing therefore the first evidence of a possible specific binding-site for colistin on albumin . 23
First RCT in the critically ill After the publication of several meta-analyses of the possible role of albumin administration , the first large RCT ( SAFE study ) evaluating the safety of human albumin in critically ill patients was concluded in 2004 . 24 The trial enrolled approximately 7000 critically ill patients , in need of volume replacement , randomised to receive either 4 % albumin or normal saline for intravascular fluid resuscitation . Mortality rate after 28 days appeared to be identical between the two groups ( relative risk of death 0.99 ; 95 % CI 0.91 – 1.09 ; p = 0.87 ). Moreover , no differences were observed among the secondary outcomes of the study . On the whole , the study concluded that , in critically ill patients , the use of either 4 % albumin or normal saline for fluid resuscitation results in similar outcomes , as originally hypothesised by the investigators , and in contrast to previous findings .
In addition to the main findings of the trial , a post hoc analysis on pre-defined subgroups identified two specific categories of patient in which a potentially different effect of the treatment applied was observed . In patients with severe sepsis , the administration of albumin was associated with a tendency towards a reduction in mortality rate ( relative risk of death 0.87 ; 95 % CI 0.74 – 1.02 , p = 0.09 ), whereas in patients with trauma the administration of albumin was observed to be associated with an increased risk of death ( relative risk of death 1.36 ; 95 % CI 0.99 – 1.86 , p = 0.06 ), especially in those with associated brain injury . 24 In both subgroups , the findings did not achieve a statistical significance , but strongly suggested two important differences in the treatment effect of albumin to be further investigated .
Traumatic brain injury Following the conclusion of the SAFE study , and the observation of possible harm of albumin administration in patients with traumatic brain injury , the same investigators performed a post hoc follow-up study on patients with traumatic brain injury at the time of randomisation . 25 After a detailed characterisation of the brain injury at baseline , 460 patients , randomised in the SAFE study to receive either 4 % albumin or crystalloids for intravascular fluid resuscitation , were followed for 24 months . Survival analysis confirmed a significant
increased risk of death associated with the use of human albumin as compared to crystalloids ( relative risk of death 1.63 ; 95 % CI 1.17 – 2.26 ; p = 0.003 ), which appeared greater in patients with severe brain injury at the time of randomisation . After a subsequent analysis , an increased intracranial pressure during the first week of treatment with albumin appeared to be the most likely mechanism associated with the increased mortality observed . 26 Although these findings have been criticised , 27 at the moment , patients with a traumatic brain injury are the first category of critically ill patients in which a specific and strong indication regarding human albumin administration has been achieved , including ultimately a ban on its use .
Severe sepsis or septic shock After the post hoc analysis on the pre-defined subgroup of patients with severe sepsis enrolled in the SAFE study , many investigators have focused their attention on the potential benefit of human albumin in severe sepsis or septic shock . 28 The Albumin Italian Outcome Sepsis ( ALBIOS ) trial , the first trial focused on this category of patients , has been completed and the results published . 16 This was an Italian multicentre , open-label RCT that enrolled 1818 patients with severe sepsis or septic shock from 100 Italian ICUs . Patients were randomised to receive either 20 % albumin and crystalloids or crystalloids alone during the first phase of volume replacement , and targeting , during the next 28 days , albumin administration to a serum albumin concentration ≥30g / l .
The primary outcome was death from any cause at 28 days and secondary outcomes were death from any cause at 90 days , number of patients with organ dysfunction , the degree of dysfunction , and length of stay in the ICU and the hospital . During the first seven days , patients in the albumin group , as compared with those in the crystalloid group , showed a higher mean arterial pressure ( p = 0.03 )
22 | 2019 | hospitalpharmacyeurope . com