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Alkaline Phosphatase in Infant Cardiopulmonary Bypass: Kinetics and Relationship to Organ Injury and Major
Jesse A Davidson1, Tracy T Urban2, Christine Baird1
1Department of Pediatrics, Children's Hospital Colorado/University of Colorado, Denver, Aurora, CO.
Insights
Alkaline phosphatase (AP) activity significantly decreases after infant cardiopulmonary bypass, particularly bone and liver isoforms. Persistent low AP activity is linked to major cardiac events and organ dysfunction in infants.
Area of Science:
- Biochemistry
- Pediatric Cardiology
- Critical Care Medicine
Background:
- Infant cardiopulmonary bypass (CPB) can impact physiological markers.
- Alkaline phosphatase (AP) is an enzyme with various isoforms, including bone and liver-derived ones.
- Understanding AP kinetics post-CPB is crucial for assessing infant outcomes.
Purpose of the Study:
- To investigate the activity and concentration changes of alkaline phosphatase (AP) and its isoforms following infant CPB.
- To determine the association between postoperative AP activity levels and major cardiovascular events, organ injury, and support requirements.
Main Methods:
- A prospective cohort study involving 120 infants (≤120 days) undergoing CPB.
- AP total and isoform-specific activity measured at 6 time points (pre-op to 72 hours post-op).
- AP concentrations and organ injury biomarkers collected up to 24 hours post-op; major cardiovascular events were tracked.
Main Results:
- AP activity decreased significantly during CPB, mainly due to reduced bone and liver-2 isoforms.
- A notable percentage of patients (27%) showed declining AP activity up to 24 hours post-op.
- Persistent low AP activity (≤80 U/L) at 72 hours was independently associated with a 5.6-fold increased risk of major cardiac events.
Conclusions:
- AP activity diminishes during and after infant CPB, influenced by bone and liver isoform levels.
- Early AP activity levels correlate with the need for vasoactive-inotropic support and markers of organ dysfunction (lactate, creatinine, NT-proBNP, IFABP).
- Sustained low AP activity post-CPB is a significant predictor of adverse cardiovascular outcomes in infants.
Objectives:
To determine the kinetics of alkaline phosphatase (AP) activity and concentration after infant cardiopulmonary bypass, including isoform-specific changes, and to measure the association between postoperative AP activity and major postoperative cardiovascular events, organ injury/dysfunction, and postoperative support requirements STUDY DESIGN: Prospective cohort study of 120 infants ≤120 days of age undergoing cardiopulmonary bypass. AP total and isoform-specific activity was assessed at 6 time points (preoperation, rewarming, 6, 24, 48, and 72 hours postoperation). Low AP activity was defined as ≤80 U/L. AP concentrations and biomarkers of organ injury/dysfunction were collected through 24 hours postoperation. Major cardiovascular events were defined as cardiac arrest, mechanical circulatory support, or death.
Results:
AP activity loss occurred primarily during the operation (median decrease 89 U/L; P < .0001) secondary to decreased bone and liver 2 isoforms. Activity declined through 24 hours in 27% of patients. AP activity strongly correlated with serum concentration (r = 0.87-0.91; P < .0001). Persistent low AP activity at 72 hours was associated independently with occurrence of a major cardiac event (OR 5.6; P < .05). Early AP activity was associated independently with subsequent vasoactive-inotropic score (P < .001), peak lactate (P < .0001), peak creatinine (P < .0005), N-terminal pro-brain natriuretic peptide (P < .05), and intestinal fatty acid binding protein (P < .005).
Conclusions:
AP activity decreases during infant cardiopulmonary bypass and may continue to decrease for 24 hours. Activity loss is secondary to decreased bone and liver 2 isoform concentrations. Early low AP activity is associated independently with subsequent postoperative support and organ injury/dysfunction, and persistence of AP activity ≤80 U/L at 72 hours is associated independently with increased odds of major cardiovascular events.
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