Albumin Administration in Brain Injury: Safety Concerns
No, albumin should NOT be administered to patients with traumatic brain injury—multiple high-quality guidelines and clinical trials demonstrate significantly increased mortality with albumin use in this population. 1, 2
Primary Evidence Against Albumin Use
The landmark SAFE study provides definitive evidence of harm: severe TBI patients receiving 4% albumin had substantially higher mortality compared to 0.9% saline (24.5% vs. 15.1%, RR: 1.62,95% CI: 1.12–2.34, p = 0.009). 1, 2 This mortality difference became even more pronounced at 2-year follow-up, with albumin-treated patients showing 41.8% mortality versus 22.2% with saline (RR: 1.88,95% CI 1.31–2.7, p < 0.001). 1, 2
Current Guideline Recommendations
Multiple authoritative guidelines explicitly recommend against albumin in TBI:
- The 2018 Anaesthesia guidelines for severe traumatic brain injury state: "We do not suggest using 4% albumin solution in severe TBI patients" (Grade 2-, Strong Agreement). 1, 2
- The European Society of Intensive Care Medicine (ESICM) does not recommend albumin after brain injury. 1, 2
- The 2024 International Collaboration for Transfusion Medicine Guidelines strongly recommends against albumin use in traumatic brain injury based on moderate quality evidence. 1, 2
- The 2024 International Multidisciplinary Perioperative Quality Initiative strongly recommends against albumin in TBI patients. 2
Mechanism of Harm
The increased mortality appears directly related to elevated intracranial pressure:
- Albumin use is associated with significantly increased ICP during the first week post-injury, with a linear increase in mean ICP compared to saline (1.30±0.33 vs. -0.37±0.36, p=0.0006). 3
- The hypotonic nature of 4% albumin infusion likely contributes to cerebral edema by reducing plasma osmolarity. 1, 2, 4
- Deaths were significantly more common when ICP monitoring was discontinued during the first week in albumin-treated patients (34.4% vs. 17.4%, p=0.006). 3
Broader Trauma Context
The harm extends beyond isolated TBI to general trauma populations: A 2015 systematic review of albumin in trauma patients found higher mortality in albumin-treated patients overall (RR, 1.35; 95% CI, 1.03-1.77). 1, 2 However, the SAFE trial subgroup analysis suggests the harm may be specific to TBI patients, as trauma patients without TBI showed no mortality difference (RR, 1.00; 95% CI, 0.56-1.79). 1
Recommended Fluid Management Instead
Use isotonic crystalloids as first-line therapy:
- 0.9% normal saline is the evidence-based alternative, demonstrating superior outcomes in TBI. 1, 2
- Isotonic crystalloids maintain normal blood volume, optimize cerebral blood flow, and avoid reduction in plasma osmolarity. 2
- Buffered isotonic solutions (such as Plasmalyte®) may be preferable to avoid hyperchloremic metabolic acidosis. 2
For intracranial hypertension specifically, use osmotherapy:
- Mannitol (0.25-0.5 g/kg IV over 20 minutes) and hypertonic saline (7.5% at 250 mL bolus over 15-20 minutes) have comparable efficacy at equiosmotic doses. 1, 5
- Mannitol is the only ICP-lowering therapy associated with improved cerebral oxygenation. 1, 5
- These agents should only be used for documented intracranial hypertension, not prophylactically. 1, 5
Critical Caveats
Avoid hypotonic solutions entirely: Hypotonic solutions should be avoided in acute brain injury due to risk of induced cerebral edema. 2 The 4% albumin solution is effectively hypotonic in the context of brain injury. 1, 4
If hemorrhagic shock coexists with TBI: Albumin is not recommended even when severe TBI is associated with hemorrhagic shock. 1
Monitor for hypoalbuminemia but don't correct it with albumin: While low serum albumin levels correlate with poor outcomes in TBI, 6 this association does not justify albumin administration given the proven harm from interventional trials. 1, 3