Early prediction of vasopressor initiation in ICU sepsis patients using an interpretable EHR-based ML model

Early identification of septic patients who will require vasopressor support could provide a critical window for hemodynamic optimisation, yet current bedside cues often appear only when shock is imminent.

We aimed to develop and validate an interpretable electronic health record (EHR)-based machine-learning model that predicts vasopressor initiation several hours before therapy in intensive care unit (ICU) patients with sepsis.

We conducted a retrospective study using the MIMIC-IV v2.2 database (2008-2019). We screened adult Sepsis-3 ICU stays and labeled the patients who commenced continuous vasopressor infusions 6 to 48 hours after admission as cases; we defined controls as sepsis patients with ICU stays ≥48 hours and no vasopressor exposure. We performed one to one nearest neighbour matching on age, sex, Charlson index, SOFA score with the cardiovascular component removed, weight, and early lactate/hematocrit availability to minimise confounding. We engineered demographic, physiological, and laboratory features measured from -6 to -2 hours relative to vasopressor initiation (or a matched time point) under multiple parameter combinations. We trained seven algorithms with Monte Carlo cross validation and evaluated performance on an independent validation set. We assessed model interpretability with Shapley values.

We analyzed 1,539 cases and 1,431 controls; the independent validation set comprised 751 stays (~25%). A Random Forest classifier achieved an area under the receiver operating characteristic (AUROC) of 0.75 (95% CI, 0.72-0.79), a sensitivity of 0.74 (95% CI, 0.69-0.78), a specificity of 0.65 (95% CI, 0.60-0.70), a precision of 0.70 (95% CI, 0.66-0.74) and a F1 score of 0.72 (95% CI, 0.68-0.75) at the Youden's index threshold. The model outperformed simple surrogates-mean blood pressure (AUROC, 0.68; 95% CI, 0.64-0.72) and modified shock index (AUROC, 0.65; 95% CI, 0.62-0.69)-and a reproduced bidirectional LSTM (AUROC, 0.73; 95% CI, 0.70-0.77). Key predictors included declining mean blood pressure at - 2 to -4 hours, elevated lactate ( > 2.5 mmol/L), and hematocrit outside 30-37%. Model alerts would occur two to four hours before vasopressor initiation, providing actionable lead time for clinicians.

This proof-of-concept study shows that routinely collected ICU data can predict impending vasopressor initiation with clinically interpretable outputs. However, these findings reflect internal validation only and should be interpreted with caution. External validation on multi-center retrospective cohorts, followed by silent-mode prospective evaluation, is warranted to confirm generalisability and to assess the real-world impact on time-to-vasopressor, fluid balance, and patient outcomes.