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INTRODUCTION: Intravenous (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. METHODS: This 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. RESULTS: FO 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). CONCLUSIONS: Using 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.
INTRODUCTION: Intravenous (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. METHODS: This 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. RESULTS: FO 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). CONCLUSIONS: Using 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.
Background: In critically ill patients, complex relationships exist among patient disease factors, medication management, and mortality. Considering the potential for nonlinear relationships and the high dimensionality of medication data, machine learning and advanced regression methods may offer advantages over traditional regression techniques. The purpose of this study was to evaluate the role of different modeling approaches incorporating medication data for mortality prediction. Methods: This was a single-center, observational cohort study of critically ill adults. A random sample of 991 adults admitted ≥ 24 hours to the intensive care unit (ICU) from 10/2015 to 10/2020 were included. Models to predict hospital mortality at discharge were created. Models were externally validated against a temporally separate dataset of 4,878 patients. Potential mortality predictor variables (n=27, together with 14 indicators for missingness) were collected at baseline (age, sex, service, diagnosis) and 24 hours (illness severity, supportive care use, fluid balance, laboratory values, MRC-ICU score, and vasopressor use) and included in all models. The optimal traditional (equipped with linear predictors) logistic regression model and optimal advanced (equipped with nature splines, smoothing splines, and local linearity) logistic regression models were created using stepwise selection by Bayesian information criterion (BIC). Supervised, classification-based ML models [e.g., Random Forest, Support Vector Machine (SVM), and XGBoost] were developed. Area under the receiver operating characteristic (AUROC), positive predictive value (PPV), and negative predictive value (NPV) were compared among different mortality prediction models. Results: A model including MRC-ICU in addition to SOFA and APACHE II demonstrated an AUROC of 0.83 for hospital mortality prediction, compared to AUROCs of 0.72 and 0.81 for APACHE II and SOFA alone. Machine learning models based on Random Forest, SVM, and XGBoost demonstrated AUROCs of 0.83, 0.85, and 0.82, respectively. Accuracy of traditional regression models was similar to that of machine learning models. MRC-ICU demonstrated a moderate level of feature importance in both XGBoost and Random Forest. Across all ten models, performance was lower on the validation set. Conclusions: While medication data were not included as a significant predictor in regression models, addition of MRC-ICU to severity of illness scores (APACHE II and SOFA) improved AUROC for mortality prediction. Machine learning methods did not improve model performance relative to traditional regression methods.
Background: Medication management in the intensive care unit (ICU) is causally linked to both treatment success and potential adverse drug events (ADEs), often associated with deleterious consequences. Patients with higher severity of illness tend to require more management. The purpose of this evaluation was to explore the effect of comprehensive medication management (CMM) on mortality in critically ill patients. Methods: In this retrospective cohort study of adult ICU patients, CMM was measured by critical care pharmacist (CCP) medication interventions. Propensity score matching was performed to generate a balanced 1:1 matched cohort, and logistic regression was applied for estimating propensity scores. The primary outcome was the odds of hospital mortality. Hospital and ICU length of stay were also assessed. Results: In a cohort of 10,441 ICU patients, the unadjusted mortality rate was 11% with a mean APACHE II score of 9.54 and Medication Regimen Complexity-Intensive Care Unit (MRC-ICU) score of 5.78. Compared with CCP interventions less than 3, more CCP interventions was associated with a significantly reduced risk of mortality (estimate -0.04, 95% confidence interval -0.06 - -0.03, p < 0.01) and shorter length of ICU stay (estimate -2.77, 95% CI -2.98 - - 2.56, p < 0.01). Conclusions: The degree by which CCPs deliver CMM in the ICU is directly associated with reduced hospital mortality independent of patient characteristics and medication regimen complexity.
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