Albumin Should Not Be Used in Patients with Traumatic Brain Injury or Acute Brain Injury Due to Increased Mortality Risk
Albumin administration is contraindicated in patients with traumatic brain injury (TBI) and should be avoided in acute brain injury, as it significantly increases mortality and worsens neurological outcomes. 1, 2
Evidence of Harm in Traumatic Brain Injury
The landmark SAFE study provides the strongest evidence against albumin use in TBI:
- Patients with severe TBI who received 4% albumin had 62% higher mortality compared to those receiving 0.9% saline (24.5% vs. 15.1%, RR: 1.62, p = 0.009). 1
- At 2-year follow-up, the mortality difference was even more pronounced (41.8% vs. 22.2%, RR: 1.88, p < 0.001). 1
- A 2015 systematic review confirmed higher mortality in albumin-treated trauma patients (RR: 1.35,95% CI: 1.03-1.77). 1
Mechanism of Harm
The hypotonic nature of 4% albumin infusion likely contributes to cerebral edema by reducing plasma osmolarity, which promotes water shift into brain tissue and worsens intracranial pressure in patients with already compromised intracranial compliance. 1, 2
Current Guideline Recommendations
Multiple authoritative guidelines explicitly recommend against albumin in brain injury:
- The 2024 International Multidisciplinary Perioperative Quality Initiative strongly recommends against albumin use in TBI patients (moderate quality evidence). 1
- The 2018 guidelines for severe TBI management state: "We do not suggest using 4% albumin solution in severe TBI patients" (Grade 2-, Strong Agreement). 1
- The European Society of Intensive Care Medicine does not recommend albumin after brain injury. 1
- European trauma guidelines from 2022 note that albumin was associated with worse neurological prognosis in prospective studies of brain injury patients. 3
Regarding Hydrocephalus Specifically
The question about hydrocephalus requires nuanced consideration:
- There is no direct evidence that albumin worsens hydrocephalus per se. The older research studies 4, 5 examine albumin kinetics in hydrocephalus but do not address whether exogenous albumin administration worsens the condition.
- However, if the hydrocephalus occurs in the context of acute brain injury or TBI, albumin remains contraindicated due to the mortality risk documented above. 1, 2
- One small 1983 study 6 suggested that 25% hypertonic albumin might reduce intracranial pressure in patients with mild-to-moderate brain edema, but this contradicts the robust evidence from the SAFE study and should not guide current practice.
Recommended Fluid Management Instead
For patients with acute brain injury or TBI requiring volume resuscitation:
- Use isotonic crystalloids (0.9% saline or buffered isotonic solutions like Plasmalyte®) as first-line therapy. 3, 1, 2
- Avoid hypotonic solutions (Ringer's lactate, Hartmann's solution) as they worsen cerebral edema and mortality. 3, 2
- For osmotherapy to treat documented intracranial hypertension, use hypertonic saline (3-7.5%) or mannitol instead. 7
Critical Pitfalls to Avoid
- Never use albumin for resuscitation in any patient with TBI or acute brain injury, regardless of hemodynamic status. 1, 2
- Do not assume albumin is safe in hydrocephalus patients if they have concurrent or recent brain injury. 1
- The one exception noted in guidelines is subarachnoid hemorrhage, where retrospective data suggested possible benefit during the high-risk period for secondary ischemia (days 5-14), though this remains controversial. 3