What are the risks of using albumin (human albumin) as a colloid in pediatric craniotomy surgery?

Risks of Albumin in Pediatric Craniotomy Surgery

Albumin should be avoided in pediatric craniotomy surgery due to a 62% increased risk of death in brain-injured patients, with isotonic saline recommended as the first-line fluid for volume replacement. 1

Primary Mortality Risk in Brain Injury

The most critical risk is increased mortality in patients with traumatic brain injury or intracranial pathology. The SAFE study demonstrated a relative risk of death of 1.62 (95% CI 1.12-2.34) in brain-injured patients receiving albumin compared to saline—a 62% increase in mortality. 1 This mortality signal was specific to brain injury, as patients without traumatic brain injury showed no difference (RR 1.00,95% CI 0.56-1.79). 1 A 2015 systematic review confirmed higher mortality in albumin-treated trauma patients (RR 1.35,95% CI 1.03-1.77), with the brain injury subgroup driving this effect. 1

Mechanism of Harm: Worsening Cerebral Edema

Albumin exacerbates cerebral edema through increased capillary leak in brain-injured patients. 1 When the blood-brain barrier is disrupted during craniotomy or from underlying pathology, albumin leaks into the cerebral interstitium, drawing fluid with it and amplifying cerebral edema rather than reducing it. 1 This contradicts the theoretical oncotic benefit and represents a critical pitfall in neurosurgical fluid management.

Guideline Recommendations Against Use

Multiple high-quality guidelines specifically recommend against albumin in pediatric neurosurgery:

• The PeriOperative Quality Initiative (2024) recommends against routine albumin use in neurosurgery, stating additional RCTs are needed to guide perioperative fluid therapy in this population. 1
• The International Collaboration for Transfusion Medicine Guidelines (2024) specifically recommend against albumin in pediatric patients undergoing cardiovascular surgery for priming bypass circuits or volume replacement (Conditional Recommendation, Very Low Certainty of Evidence). 1, 2
• The Dutch Pediatric Society (2006) recommends isotonic saline as first-choice fluid for initial resuscitation in neonates and children with hypovolemia (Grade A recommendation). 3, 1

Additional Safety Concerns Specific to Pediatrics

Beyond mortality, albumin carries multiple risks in the pediatric neurosurgical population:

• Coagulation impairment: In small infants (3-15 kg), albumin 5% significantly decreased clot firmness and impaired multiple thromboelastography parameters, though effects were less severe than with hydroxyethyl starch. 4
• Anaphylaxis risk: Albumin carries inherent risk of allergic reactions. 1, 2
• Fluid overload: Particularly dangerous if infused >2 mL/min, leading to pulmonary edema. 1, 2
• Hypotension: Paradoxical hypotension can occur despite volume expansion. 1, 2
• Hemodilution: May necessitate RBC transfusion. 1, 2

Lack of Efficacy Evidence

No randomized controlled trials demonstrate benefit of albumin over crystalloids in pediatric neurosurgery or craniotomy specifically. 1 The 2024 guidelines acknowledge this evidence gap, noting that the role of albumin during major surgery needs further investigation. 1 In preterm neonates, albumin showed no benefit for volume replacement (RR for mortality 1.36,95% CI 0.69-2.66). 1

Recommended Alternative: Isotonic Crystalloids

Isotonic crystalloids (0.9% saline) are the evidence-based first-line therapy:

• Isotonic solutions (280-310 mOsm/L) prevent cerebral edema risk, which is paramount in craniotomy patients. 1
• Isotonic crystalloids reduce mortality and improve neurological prognosis in acute brain injury (GRADE 2+ recommendation). 1
• The volume ratio of albumin to saline needed for equivalent hemodynamic effect is only 1.4:1, making the theoretical volume advantage minimal. 1
• Cost differential is substantial: Albumin costs approximately $130 per 25g versus $1.50 per liter for isotonic saline, without proven superiority. 1, 2

Clinical Algorithm for Pediatric Craniotomy Fluid Management

1. Use isotonic saline (0.9% NaCl) as first-line fluid for all volume replacement needs. 1
2. Administer initial bolus of 10-20 mL/kg, with repeated doses based on hemodynamic response. 1
3. Monitor for adequate perfusion using clinical parameters and hemodynamic monitoring as appropriate for age. 1
4. If massive volume requirements develop, consider blood products rather than colloids given the surgical context. 1

Critical Pitfall to Avoid

Never administer albumin to "correct" a low preoperative albumin level in craniotomy patients. 1, 2 Low serum albumin is a prognostic marker of illness severity, not a treatment target. 2, 5 While preoperative hypoalbuminemia is associated with increased odds of mortality (OR 1.91,95% CI 1.41-2.60) and nonroutine hospital discharge (OR 1.46,95% CI 1.21-1.76) in craniotomy patients, 5 albumin infusion does not improve these outcomes and potentially increases mortality in this population. 1, 2

Summary of Evidence Quality

The recommendation against albumin is based on:

• High-quality RCT data from the SAFE study showing harm in brain injury 1
• Multiple recent guidelines (2024-2025) from major societies recommending against use 1, 2
• Consistent meta-analytic evidence showing no benefit and potential harm 3, 1
• Absence of any pediatric neurosurgery-specific trials demonstrating benefit 1