Evidence Against the Use of Albumin in Traumatic Brain Injury
Albumin should not be used for fluid resuscitation in patients with traumatic brain injury due to significantly increased mortality risk. 1
Key Evidence Against Albumin in TBI
The SAFE (Saline versus Albumin Fluid Evaluation) study, which recruited nearly 7,000 patients, found that severe TBI patients who received 4% albumin solution had significantly higher mortality rates compared to those receiving 0.9% saline (24.5% vs. 15.1%, RR: 1.62, CI 95%: 1.12–2.34, p = 0.009) 1
A 2-year follow-up subgroup analysis of the SAFE study with 460 TBI patients showed an even more pronounced increased risk of mortality with albumin administration (41.8% vs. 22.2%, RR: 1.88,95% CI 1.31–2.7, p < 0.001) 1
The 2024 International Multidisciplinary Perioperative Quality Initiative strongly recommends against the use of albumin in patients with traumatic brain injury based on moderate quality evidence 1
A 2015 systematic review of albumin use in trauma patients found a higher mortality in albumin-treated patients (RR, 1.35; 95% CI, 1.03-1.77) 1
Mechanisms of Harm
Increased Intracranial Pressure
Research has identified that albumin administration is associated with a significant linear increase in mean intracranial pressure (ICP) during the first week after TBI compared to saline 2
This increased ICP is the most likely mechanism for the higher mortality observed in TBI patients receiving albumin 2
The hypotonic nature of 4% albumin infusion may have played a role in worsening outcomes by contributing to cerebral edema 1
Fluid Management Considerations
In TBI patients, the primary goal for fluid therapy is to maintain normal blood volume, optimize cerebral blood flow, and avoid reduction in plasma osmolarity 1
Hypotonic solutions should be avoided in patients with acute brain injury due to the risk of induced cerebral edema 1
Isotonic crystalloids are recommended as first-line fluid therapy in patients with acute brain injury to reduce mortality and improve neurological prognosis 1
Expert Recommendations
The European Society of Intensive Care Medicine (ESICM) does not recommend using albumin solution after brain injury 1
Current guidelines from the International Collaboration for Transfusion Medicine Guidelines highlight the potential harm of albumin specifically in TBI patients 1
The 2018 guidelines for management of severe traumatic brain injury explicitly state: "We do not suggest using 4% albumin solution in severe TBI patients" (Grade 2-, Strong Agreement) 1
Alternative Approaches
For osmotherapy to treat intracranial hypertension, mannitol and hypertonic saline have comparable efficacy at equiosmotic doses (about 250 mOsm) 1
Isotonic crystalloids, particularly 0.9% saline, are recommended as the first-line fluid therapy for TBI patients 1
Buffered isotonic solutions (such as Plasmalyte®) might be preferable to 0.9% saline as they are not associated with hyperchloremic metabolic acidosis or adverse renal effects 1
Research Limitations and Controversies
While most evidence shows harm with 4% (hypooncotic) albumin, some limited research suggests that hyperoncotic (20-25%) albumin might have different effects 3
A narrative review and meta-analysis of hyperoncotic albumin in the Lund concept of TBI treatment showed potentially reduced mortality, but this evidence has a high risk of bias and requires prospective randomized controlled trials 3
Despite some observational studies suggesting that low serum albumin levels correlate with poor outcomes in TBI, the administration of exogenous albumin for correction appears to worsen rather than improve outcomes 4, 5
In conclusion, the preponderance of evidence strongly advises against the use of albumin for fluid resuscitation in TBI patients, with multiple high-quality guidelines and studies demonstrating increased mortality risk compared to crystalloid solutions.