What outcomes should be assessed in pediatric patients with underlying medical conditions, such as congenital heart disease or impaired renal function, undergoing craniotomy surgeries and treated with albumin (human albumin) as a colloid?

Outcomes to Assess in Pediatric Craniotomy Studies Evaluating Albumin

Studies evaluating albumin use in pediatric craniotomy patients must prioritize 30-day all-cause mortality as the primary endpoint, given the 62% increased risk of death demonstrated in brain-injured patients receiving albumin (RR 1.62,95% CI 1.12-2.34). 1, 2

Primary Outcome

Mortality

• 30-day all-cause mortality should be the primary endpoint, as this represents the most clinically meaningful outcome where albumin has demonstrated potential harm specifically in brain injury populations 1
• The SAFE study's traumatic brain injury subgroup analysis provides the strongest evidence that mortality is the critical safety outcome requiring assessment in any neurosurgical population 1, 2
• Stratify mortality analysis by traumatic versus non-traumatic craniotomy, as the mortality signal with albumin was specific to traumatic brain injury patients 1

Critical Secondary Outcomes

Neurological Function and Brain Injury Markers

• Cerebral edema severity assessed by CT/MRI imaging is particularly important in craniotomy patients, as albumin can worsen cerebral edema through increased capillary leak when the blood-brain barrier is disrupted 1, 2
• New major neurological deficits occurring within 30 days postoperatively, which occur in approximately 5.0% of pediatric craniotomy patients 3
• Neurological prognosis scores at discharge and 30 days, as albumin showed worse neurological outcomes in subarachnoid hemorrhage patients 2
• Karnofsky Performance Index (KPI) at discharge and 30 days, as preoperative KPI and new neurological deficits are the most powerful predictors of functional outcome in pediatric craniotomy 3

Hemodynamic and Resuscitation Efficacy

• Total volume of fluid administered in the first 24 hours (both colloid and crystalloid combined) reflects the efficacy of albumin for volume expansion 1
• Number of fluid boluses required to achieve hemodynamic stability, defined by normalized heart rate, adequate perfusion, and urine output >0.5-1 mL/kg/hour 1
• Time to hemodynamic stability from initial fluid administration 1
• Mean arterial pressure maintenance ≥65 mmHg or age-appropriate targets in younger children 1
• The volume ratio comparison is relevant since albumin to saline equivalence is only 1.4:1, making the theoretical volume advantage minimal 1, 2

Renal Outcomes

• Acute kidney injury using pediatric KDIGO criteria is essential, as albumin showed no benefit in preventing renal replacement therapy in critically ill adults (RR 1.11,95% CI 0.96-1.27) 1
• Need for renal replacement therapy during hospitalization 1
• Urine output in first 48 hours postoperatively 1
• This is particularly critical in pediatric patients with pre-existing impaired renal function 1

Respiratory Outcomes

• Pulmonary edema incidence, though meta-analyses showed no difference between crystalloid and colloid (pooled RR 0.84,95% CI 0.25-2.45), this remains important in the context of brain injury where fluid management is critical 4, 1
• Duration of mechanical ventilation 4
• Rates of respiratory dysfunction, as children treated with albumin boluses showed higher rates of respiratory dysfunction in the FEAST trial 4

Safety and Adverse Events

• Fluid overload requiring diuretic therapy, especially if albumin infused >2 mL/min 1, 2
• Hypotension episodes requiring vasopressor support 1
• Anaphylaxis incidence 2
• Hemodilution requiring RBC transfusion 2
• Hyperchloremic acidosis, which occurred at higher rates in children receiving fluid boluses 4

Surgical and Hospital Outcomes

• Length of intensive care unit stay 5
• Total hospital length of stay 6
• Surgical site infections, which occur more frequently in obese patients undergoing craniotomy 7
• Need for ventricular shunting or endoscopic ventriculostomy, which is necessary in 11.3% of pediatric craniotomy patients 3
• Discharge disposition (routine versus nonroutine hospital discharge) 7

Special Considerations for High-Risk Subgroups

Patients with Congenital Heart Disease

• Cardiac index measurements, as these patients have unique hemodynamic considerations 5
• Blood component use and transfusion requirements 5
• Postoperative infection rates, as preoperative albumin concentrations <3.0 g/dL are associated with increased postsurgical infection in pediatric cardiac surgery patients 8

Patients with Impaired Renal Function

• Baseline and serial creatinine measurements 1
• Fluid balance calculations 5
• Electrolyte abnormalities, particularly hyperchloremia 4

Critical Methodological Pitfall to Avoid

Do not use serum albumin normalization as an outcome measure—correcting low preoperative albumin levels with albumin infusion does not improve outcomes and may increase mortality in brain-injured patients, making this a misleading endpoint 1, 2. Low albumin is a prognostic marker, not a treatment target 2. While preoperative hypoalbuminemia (<3.5 g/dL) is associated with increased mortality and nonroutine discharge in craniotomy patients 7, and levels <3.0 g/dL predict worse outcomes in pediatric cardiac surgery 8, administering albumin to correct these levels has not been shown to improve outcomes and carries specific risks in neurosurgical populations 1, 2.

Evidence Quality Considerations

The 2024 International Collaboration for Transfusion Medicine Guidelines specifically recommend against albumin in pediatric patients undergoing cardiovascular surgery (Conditional Recommendation, Very Low Certainty of Evidence) 4, and the PeriOperative Quality Initiative (2024) recommends against routine albumin use in neurosurgery 2. The Dutch Pediatric Society recommends isotonic saline as first-choice fluid for initial resuscitation in children with hypovolemia (Grade A recommendation) 4, 2. These guideline recommendations should frame the study design, with outcomes selected to detect both potential harms and any theoretical benefits of albumin in this specific population.