Deep learning guided propofol ketamine dosing and inflammation trajectories in elderly burns.

Background and objectives: Elderly patients (≥65 years) who sustain burn injuries encounter a clinically significant perioperative challenge: a dysregulated hyperinflammatory response, characterized by elevated levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP), compounded by a markedly reduced hemodynamic reserve. Both propofol and low-dose ketamine exhibit distinct anti-inflammatory mechanisms; however, the optimization of their combined dosing within explicit safety parameters remains unestablished. Our objectives were to: (1) develop and externally validate a probabilistic machine learning (ML) model to predict dynamic 24-h trajectories of inflammatory markers; and (2) integrate these predictions with a safety-constrained offline reinforcement learning (RL) agent to formulate individualized propofol-ketamine dosing recommendations. Study design: This study employed a retrospective multi-cohort analysis utilizing two publicly accessible intensive care databases. Setting: The research was conducted in an academic medical center ICU (MIMIC-IV) and across 208 community and academic hospitals (eICU Collaborative Research Database). Measurements: The study analyzed 614 perioperative episodes in patients aged ≥65 years with confirmed burn injuries who received propofol-based anesthesia for ≥30 min and had ≥2 inflammatory laboratory measurements within 6-24 h post-induction. External validation was performed on 206 independent episodes. Main results: The proposed Event-Transformer with continuous-time Neural ODE dynamics demonstrated a 12-h IL-6 mean absolute error (MAE) of 6.82 pg/mL, representing a 70.1% improvement over linear mixed models (22.8 pg/mL). It achieved an inflammatory spike detection area under the receiver operating characteristic curve (AUROC) of 0.814 and empirical 90% prediction interval (PI) coverage of 87.2%. The Conservative Policy with Q-Learning (CPQL) dosing agent enhanced the time within the MAP target range (65-90 mmHg) from 62.3% to 71.8% ( Conclusions: An integrated inflammatory forecasting and dosing optimization pipeline can facilitate individualized propofol-ketamine titration in elderly burn patients, yielding predicted clinically significant improvements in hemodynamic stability and inflammatory burden, without safety violations. Clinically, the 70.1% reduction in IL-6 forecasting error translates to a meaningful difference between correct and incorrect inflammatory spike classification in a substantial fraction of patients, supporting the potential real-world utility of this framework as a decision-support tool to inform and guide future prospective trials.