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Hyperlactatemia in Critically Ill Children: Modeling Early Recovery Kinetics After Initiation of Extracorporeal
Cheuk C Au1,2, Frederick Vonberg1,3, Matthew Luchette1
1Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA.
Insights
High blood lactate levels in critically ill children on ECMO indicate impaired lactate clearance. Mathematical modeling revealed that severe impairment of lactate clearance, not increased production, drives elevated lactate during critical illness.
Area of Science:
- Pediatric critical care medicine
- Biomedical engineering
- Mathematical modeling in medicine
Background:
- Blood lactate concentration ([Lac]b) is a key indicator of metabolic status in critically ill patients.
- Extracorporeal membrane oxygenation (ECMO) is a life-support measure for severe cardiopulmonary failure.
- Observed improvements in [Lac]b after ECMO initiation and vasopressor withdrawal prompted this investigation.
Purpose of the Study:
- To develop a mathematical model describing blood lactate recovery kinetics in pediatric ECMO patients.
- To investigate the relationship between peak [Lac]b and parameters of lactate production, transfer, and clearance (Cl[Lac]).
Main Methods:
- Retrospective analysis of 25 pediatric ECMO patients.
- Serial [Lac]b measurements during the initial 30 hours of ECMO.
- Development and application of a one-compartment, bi-exponential kinetic model.
Main Results:
- Peak [Lac]b at ECMO initiation averaged 16.7 mmol/L.
- The model estimated initial lactate load at 17.7 mmol/kg and Cl[Lac] at 19.7 mL/min.
- High initial [Lac]b strongly correlated with severely impaired Cl[Lac], with lactate production and clearance balancing at steady state.
Conclusions:
- In critically ill children requiring ECMO, elevated initial [Lac]b signifies severely reduced lactate clearance capacity.
- The developed mathematical model provides insights into lactate kinetics during critical illness.
- This modeling approach may be valuable for assessing lactate dynamics in various critical care settings.
Objectives:
Blood lactate concentration ([Lac] b ) reflects the balance among production, clearance (C l[Lac] ), and volume of distribution. We have observed dramatic improvement in [Lac] b in critically ill patients after starting support with extracorporeal membrane oxygenation (ECMO) and discontinuing vasopressors. Here, we evaluated such [Lac] b profiles to develop a mathematical model of recovery kinetics. We then examined the interrelationships between maximum [Lac] b and model-derived parameters of lactate production, endogenous lactate transfer, and C l[Lac] .
Design:
Mathematical modeling using a convenience sample.
Setting:
Quaternary U.S. academic children's hospital.
Participants:
A retrospective sample of 25 ECMO patients (from birth to < 18 yr) with serial [Lac] b measurements during the first 30 hours after initiation of ECMO.
Interventions:
None.
Measurement And Main Results:
The median (interquartile range [IQR]) age of ptients was 17 days (IQR 3-152 d), and the median weight was 3.3 kg (IQR 2.7-4.7 kg). At the initiation of ECMO, the mean peak [Lac] b was 16.7 mmol/L (95% CI, 14.3-20.0 mmol/L). Recovery in [Lac] b could be described using a one-compartment, bi-exponential, open model of kinetics. Solving the model equation showed starting lactate load was 17.7 mmol/kg (95% CI, 14.6-20.7 mmol/kg) and C l[Lac] was 19.7 mL/min (95% CI, 3.0-36.4 mL/min). The interrelationship between maximum [Lac] b and model-derived parameters in children requiring ECMO at the limits of cardiopulmonary survival showed: 1) lactate production ranged from 2.3 to 6.4 µmol/kg/min (95% CI), 2) initial endogenous lactate transfer velocity, 82.5-1301.0 µmol/kg/min, 3) high initial [Lac] b levels suggested severely impaired C l[Lac] , 4) a strong correlation was observed between model-derived velocity and transfer parameters (rho 0.75; p < 0.0001), at levels exceeding those seen in high-intensity endurance exercise, and 5) upon achieving steady state, lactate production and C l[Lac] were balanced.
Conclusions:
At the time of maximal cardiopulmonary instability requiring ECMO initiation, our model of [Lac] b recovery indicated that high initial [Lac] b reflected severely impaired and reduced C l[Lac] . This modeling approach may also be applicable to assessing changes in lactate kinetics in other forms of critical illness.
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