Modeling Patient-specific Apnea-bradycardia Patterns in Preterm Newborn.

OBJECTIVE: Preterm infants are particularly exposed to severe cardio-respiratory events, associating apnea with bradycardia and oxygen desaturation. A patient-specific and event-specific model-based approach is proposed in this work to analyze the acute heart rate response to apnea-bradycardia events in preterm newborn. METHODS: A novel model integrating the main cardio-respiratory interactions which are specific to the neonatal period is proposed. An evolutionary algorithm is applied to estimate patient-specific model parameters from a database of 37 apnea-bradycardia episodes acquired from 10 preterm newborns. Unsupervised clustering (K-means) was applied to the identified parameters to define phenogroups of cardio-respiratory responses to apnea. RESULTS: A significant correspondence was observed between simulated and experimental heart rate series in all identifications (median RMSE = 8.85 bpm). Three clusters of parameters were found and were associated to three different pathophysiological dynamics related to apnea-bradycardia. CONCLUSION AND SIGNIFICANCE: The proposed method, based on patient and event-specific model parameter identification, provides a novel approach to characterize bradycardia dynamics in response to apnea, opening the way to the proposal of new personalized diagnosis and treatment possibilities in this particularly sensitive population.

Parametric analysis of an integrated cardio-respiratory model in preterm newborns during apnea.

The analysis of the complex interactions involved in the acute physiological response to apnea-bradycardia events in preterm newborns remains a challenging task. This paper presents a novel integrated model of cardio-respiratory interactions, adapted to preterm newborns. A sensitivity analysis, based Morris' screening method, was applied to study the effects of physiological parameters on heart rate and desaturation, during the simulation of a 15-seconds apnea-bradycardia episode. The most sensitive parameters are associated with fundamental, integrative physiological mechanisms involving: (i) respiratory mechanics (intermediate airways and lung compliance), (ii) fraction of inspired oxygen, (iii) metabolic rates (oxygen consumption rate), (iv) heart rate regulation and (v) chemoreflex (gain). Results highlight the relevant influence of physiological variables, involved in preterm apnea-bradycardia events.

Sensitivity Analysis of a Cardio-respiratory Model in Preterm Newborns for the Study of Patent Ductus Arteriosus.

This paper proposes an integrated model of cardio-respiratory interactions in preterm newborns, focused on the study of the patent ductus arteriosus (PDA). A formal model parameter sensitivity analysis on blood flow through the PDA is performed. Results show that the proposed model is capable of simulating hemodynamics in right-to-left and left-to-right shunts. For both configurations, the most significant parameters are associated with mechanical ventricular properties and circulatory parameters related to left ventricle loading conditions. These results highlight important physiological mechanisms involved in PDA and provide key information towards the definition of patient-specific parameters.