Human albumin : benefits in the ICU
There is a strong justification for the use of human albumin in critically ill patients and this article provides an overview of the physiological basis and supportive clinical evidence behind this rationale
The administration of human albumin as a treatment in critically ill patients has led to considerable debate over the last 20 years . 1 Despite the undeniable importance of this protein in human physiology , a large meta-analysis of 30 randomized controlled trials ( RCTs ) conducted by the Cochrane Injuries Group Albumin Reviewers in 1998 showed an increased risk of death with albumin treatment among patients with hypovolemia , burns , or hypoalbuminemia . 2 A subsequent meta-analysis of 55 RCTs in 2001 demonstrated the safety of albumin but no effect on mortality ; and further concluded that “ any such effect on mortality may be small ”. 3 Lack of well-designed RCTs and heterogeneous population among critically ill patients probably explain such contradictory conclusions and observations . A relevant endpoint would be to assess the morbidity that occurs with the use of different resuscitation fluids . 4 A meta-analysis in 2004 of 71 RCTs including 3782 patients with various critical illnesses showed a lower morbidity among patients treated with albumin ( risk ratio , RR = 0.92 , 95 % CI 0.86 – 0.98 ). 4 This protective effect of albumin was stronger when 20 studies were analyzed where the control group did not receive any albumin at all ( RR = 0.77 , 95 % CI 0.67 – 0.88 ).
Thus , to fully understand whether human albumin may be beneficial within the intensive care setting , requires an appropriate strategy to identify the specific patient categories who are most likely to benefit from treatment . In addition , because the efficacy of albumin may be related to unveiled secondary functions , further research is warranted to pinpoint which of these functions are clinically relevant . It is therefore worth summarizing the physiological role of albumin and the available clinical evidence supporting its potential benefits or harms in critically ill patients .
Primary functions Use in critically ill patients Human albumin has a crucial role in regulating the homeostasis of the intravascular blood compartment and it is reasonable to consider this molecule as relevant for the hemodynamic management of critically ill patients , especially when dealing with fluid resuscitation and management . Being a natural colloid , albumin-containing solutions are generally considered better for intravascular volume replacement compared with crystalloids , and similarly less prone to accumulation within the interstitial space . 5 Although the classical view by Ernest Starling on the compartments ’ model has recently been questioned , 6 the biological rationale for considering volume replacement with colloids more effective than with crystalloids still stands . This argument becomes even more relevant in light of the evidence of an increased risk of acute renal injury , bleeding and ultimately death , which accompanies the administration of hydroxyethyl starches , one of the most commonly used synthetic colloids . 7 , 8
The Saline versus Albumin Fluid Evaluation ( SAFE ) study published in 2004 was the first large RCT to examine the impact of saline or albumin as a fluid resuscitation on mortality . 9 The study enrolled approximately 7000 critically ill patients in need of volume replacement , who were randomized to either 4 % albumin or normal saline and the primary outcome was death from any cause within 28 days after randomization . The results showed no difference , prompting the authors to conclude that neither fluid was superior . Nevertheless , and despite no obvious benefits , in a subsequent post hoc analysis of pre-defined subgroups , the same authors identified two specific categories of patient for which albumin treatment produced opposing outcomes . In the first group , patients with severe sepsis , albumin administration was associated with a significantly reduced odds of mortality ( odds ratio , OR = 0.71 , 95 % CI 0.52 – 0.97 , p = 0.03 ) compared with those using saline . 10 The second group of patients were those with traumatic brain injury . A total of 460 patients from the original SAFE trial were followed-up for a period of 24 months at which point , the risk of death was significantly higher in patients who had received albumin ( relative risk , RR = 1.63 , 95 % CI 1.17 – 2.26 , p = 0.003 ). Furthermore , amongst those with severe brain injury , the risk of death was even higher ( RR = 1.88 ; 95 % CI 1.31 – 2.70 , p < 0.001 ). 11 In a subsequent analysis , Cooper et al 12 intimated that an increased intracranial pressure during the first week of treatment with albumin appeared to be the most likely mechanism behind the observed higher mortality . Other workers have proposed that the osmolality of the infusion fluid was a more relevant factor and because 4 % albumin is a hypo-osmolar solution , this would likely increase brain volume and intracranial pressure . 13
Severe sepsis or septic shock Since the post hoc analysis of patients with severe sepsis enrolled in the SAFE study , investigators have focused on the potential benefit of albumin in severe sepsis or septic shock . The potential benefits of albumin in sepsis syndrome may be related to its antioxidant capacity . In a study of critically ill patients , infusion of albumin led to an increase in the plasma thiol pool ( and hence antioxidant
hospitalpharmacyeurope . com | 2023 | 17