Unsupervised machine learning analysis to identify patterns of ICU medication use for fluid overload prediction
Authors: Keats Kelli , Deng Shiyuan , Chen Xianyan , Zhang Tianyi , Devlin John W. , Murphy David J. , Smith Susan E. , Murray Brian , Kamaleswaran Rishikesan , Sikora Andrea 
Published: March 2024

ABSTRACTINTRODUCTIONIntravenous (IV) medications are a fundamental cause of fluid overload (FO) in the intensive care unit (ICU); however, the association between IV medication use (including volume), administration timing, and FO occurrence remains unclear.METHODSThis retrospective cohort study included consecutive adults admitted to an ICU ≥72 hours with available fluid balance data. FO was defined as a positive fluid balance ≥7% of admission body weight within 72 hours of ICU admission. After reviewing medication administration record (MAR) data in three-hour periods, IV medication exposure was categorized into clusters using principal component analysis (PCA) and Restricted Boltzmann Machine (RBM). Medication regimens of patients with and without FO were compared within clusters to assess for temporal clusters associated with FO using the Wilcoxon rank sum test. Exploratory analyses of the medication cluster most associated with FO for medications frequently appearing and used in the first 24 hours was conducted.RESULTSFO occurred in 127/927 (13.7%) of the patients enrolled. Patients received a median (IQR) of 31 (13-65) discrete IV medication administrations over the 72-hour period. Across all 47,803 IV medication administrations, ten unique IV medication clusters were identified with 121-130 medications in each cluster. Among the ten clusters, cluster 7 had the greatest association with FO; the mean number of cluster 7 medications received was significantly greater in patients in the FO cohort compared to patients who did not experience FO (25.6 vs.10.9. p<0.0001). 51 of the 127 medications in cluster 7 (40.2%) appeared in > 5 separate 3-hour periods during the 72-hour study window. The most common cluster 7 medications included continuous infusions, antibiotics, and sedatives/analgesics. Addition of cluster 7 medications to a prediction model with APACHE II score and receipt of diuretics improved the ability for the model to predict fluid overload (AUROC 5.65, p =0.0004).CONCLUSIONSUsing ML approaches, a unique IV medication cluster was strongly associated with FO. Incorporation of this cluster improved the ability to predict development of fluid overload in ICU patients compared with traditional prediction models. This method may be further developed into real-time clinical applications to improve early detection of adverse outcomes.KEY POINTSQuestionsCan machine learning detect the presence of time-dependent medication administration patterns that are associated with risk of fluid overload in critically ill patients?FindingsUsing unsupervised machine learning, a unique IV medication cluster was identified that, when combined with the APACHE II score and diuretic use, improved the ability to predict fluid overload in ICU patients.MeaningThese findings suggest that machine learning may be an important tool for analyzing IV mediation administration patterns to predict development of fluid overload. Such models may provide insight into areas where medication administration practices could be optimized to mitigate the risk of fluid overload in this patient population.