Mechanism of Albumin-Induced Increased Intracranial Pressure in Traumatic Brain Injury
The primary mechanism by which albumin increases intracranial pressure (ICP) in traumatic brain injury patients is through its hypotonic nature, which contributes to cerebral edema by altering osmolality rather than through colloid osmotic pressure effects. 1, 2
Pathophysiological Mechanism
- The hypotonic nature of 4% albumin solution plays a critical role in worsening outcomes by contributing to cerebral edema in TBI patients 1
- Dysfunction of the neurovascular unit ("blood-brain barrier") is common in TBI, resulting in maldistribution of water and osmoles within the brain 2
- The measured in-vitro osmolality of human albumin solutions is hypo-osmolar, which can increase brain volume and intracranial pressure 2
- The osmolality of an infusion solution, rather than the colloid osmotic pressure itself, appears to be the key determinant in the pathogenesis of cerebral edema formation 2
Evidence from Clinical Studies
- The SAFE study demonstrated significantly higher mortality rates in severe TBI patients receiving 4% albumin solution compared to those receiving 0.9% saline (24.5% vs. 15.1%) 1
- A 2-year follow-up subgroup analysis showed an even more pronounced increased risk of mortality with albumin administration (41.8% vs. 22.2%) 1
- A 2013 study analyzing ICP monitoring data from SAFE study patients found a significant linear increase in mean ICP in the albumin group compared to saline during the first week after injury 3
Temporal Pattern of ICP Elevation
- The albumin-induced increase in ICP is most pronounced during the first week after traumatic brain injury 3
- When ICP monitoring was discontinued during the first week, there was a significant linear increase in mean ICP in the albumin group compared with saline (1.30±0.33 vs. -0.37±0.36, p=0.0006) 3
- This temporal pattern correlates with higher mortality in the albumin group during the first week (34.4% vs. 17.4%, p=0.006) 3
Clinical Implications and Recommendations
- The European Society of Intensive Care Medicine (ESICM) does not recommend using albumin solution after brain injury 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" 1
- For osmotherapy to treat intracranial hypertension, mannitol and hypertonic saline have comparable efficacy and are preferred options 1
- Isotonic crystalloids, particularly 0.9% saline, are recommended as first-line fluid therapy for TBI patients 1
Important Caveats
- Serum sodium and osmolality measurements are poor surrogates for direct ICP measurements in TBI patients treated with hyperosmolar therapy 4
- Initial ICP is not significantly correlated with serum sodium or osmolality, suggesting these are not useful initial clinical markers for ICP estimation 4
- The use of albumin for resuscitation in TBI patients has decreased in clinical practice, with a 2020 Australian study showing only 6.9% of severe TBI patients received albumin 5