HPE Human Albumin Update | Page 18

Study

Patients

Sample

size

794

< 6 hours

20 % albumin versus 0.9 % NaCl ( open-label )

1808 *

< 8 hours

5 % albumin versus 0.9 % NaCl ( double-blind )

360 *

< 6 hours

4 % albumin versus Ringer Lactate ( double-blind )

16

human albumin , two different studies , one in patients with severe sepsis and the other in patients with acute lung injury , have reported increased plasma thiol levels after albumin supplementation . ¹ 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 . Finally , 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 . ^{3 , 14}

First RCT in the critically ill After the publication of several metaanalyses of the possible role of albumin administration , the first large RCT evaluating the safety of human albumin in critically ill patients was concluded in 2004 . ¹⁵ 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 ( see Table 1 ). 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 , therefore , 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 , suggesting potential harm related to human albumin administration .

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 . ¹⁵ In both subgroups , the findings did not achieve a statistical significance , but strongly suggested two important differences in the treatment effect 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 . ¹⁶ 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 . ¹⁷ Although these findings have been criticised , ¹⁸ 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 at the end a ban on its use .

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