Use of Hyperoncotic Human Albumin Solution in Severe Traumatic Brain Injury Revisited-A Narrative Review and Meta-Analysis

Abstract

A significant proportion of patients with a severe traumatic brain injury (TBI) have hypoalbuminemia and require fluid resuscitation. Intravenous fluids can have both favorable and unfavorable consequences because of the risk of hyperhydration and hypo- or hyperosmolar conditions, which may affect the outcome of a TBI. Fluid resuscitation with human albumin solution (HAS) corrects low serum albumin levels and aids in preserving euvolemia in non-brain-injured intensive care units and in perioperative patients. However, the use of HAS for TBI remains controversial. In patients with TBI, the infusion of hypooncotic (4%) HAS was associated with adverse outcomes. The side effects of 4% HAS and the safety and efficacy of hyperoncotic (20-25%) HAS used in the Lund concept of TBI treatment need further investigation. A nonsystematic review, including a meta-analysis of controlled clinical trials, was performed to evaluate hyperoncotic HAS in TBI treatment. For the meta-analysis, the MEDLINE and EMBASE Library databases, as well as journal contents and reference lists, were searched for pertinent articles up to March 2021. Four controlled clinical studies involving 320 patients were included. The first was a randomized trial. Among 165 patients treated with hyperoncotic HAS, according to the Lund concept, 24 (14.5%) died vs. 59 out of 155 control patients (38.1%). A Lund concept intervention using hyperoncotic HAS was associated with a significantly reduced mortality (p = 0.002). Evidence of the beneficial effects of fluid management with hyperoncotic HAS on mortality in patients with TBI is at a high risk of bias. Prospective randomized controlled trials are required, which could lead to changes in clinical practice recommendations for fluid management in patients with TBI.

Keywords: albumin; brain injury; intracranial pressure; oncotic pressure; resuscitation.

Figure 1

Meta-analysis of mortality in controlled clinical studies from Eker et al [23,24,43,44,45], Howells et al. [49], Liu et al. [47], and Dizdarevic et al. [48] comparing the intracranial pressure-targeted Lund concept treatment, including albumin infusion, with cerebral perfusion pressure-targeted therapy of severe traumatic brain injury in adults. A random effects model was used for the analysis. The size of the squares indicates the data points from the individual studies scaled according to the percentage of the total weight (with individual trial weights equaling the proportion of total patients receiving Lund concept treatment multiplied by the number of deaths in the cerebral perfusion pressure-targeted group), and the diamond indicates the pooled findings. The dashed line indicates pooled relative risk. The proportion of the variation attributable to heterogeneity (I2) was 38.6% (95% CI, 0.0–79.0%). CPP, cerebral perfusion pressure; CI, confidence interval.