Counterfactual Sepsis Outcome Prediction Under Dynamic and Time-Varying Treatment Regimes.

Sepsis is a life-threatening condition that occurs when the body's normal response to an infection is out of balance. A key part of managing sepsis involves the administration of intravenous fluids and vasopressors. In this work, we explore the application of G-Net, a deep sequential modeling framework for g-computation, to predict outcomes under counterfactual fluid treatment strategies in a real-world cohort of sepsis patients. Utilizing observational data collected from the intensive care unit (ICU), we evaluate the performance of multiple deep learning implementations of G-Net and compare their predictive performance with linear models in forecasting patient outcomes and trajectories over time under the observational treatment regime. We then demonstrate that G-Net can generate counterfactual prediction of covariate trajectories that align with clinical expectations across various fluid limiting regimes. Our study demonstrates the potential clinical utility of G-Net in predicting counterfactual treatment outcomes, aiding clinicians in informed decision-making for sepsis patients in the ICU.

Frequency of screening and SBT Technique Trial-North American Weaning Collaboration (FAST-NAWC): an update to the protocol and statistical analysis plan.

BACKGROUND: This update summarizes key changes made to the protocol for the Frequency of Screening and Spontaneous Breathing Trial (SBT) Technique Trial-North American Weaning Collaborative (FAST-NAWC) trial since the publication of the original protocol. This multicenter, factorial design randomized controlled trial with concealed allocation, will compare the effect of both screening frequency (once vs. at least twice daily) to identify candidates to undergo a SBT and SBT technique [pressure support + positive end-expiratory pressure vs. T-piece] on the time to successful extubation (primary outcome) in 760 critically ill adults who are invasively ventilated for at least 24 h in 20 North American intensive care units. METHODS/DESIGN: Protocols for the pilot, factorial design trial and the full trial were previously published in J Clin Trials ( https://doi.org/10.4172/2167-0870.1000284 ) and Trials (https://doi: 10.1186/s13063-019-3641-8). As planned, participants enrolled in the FAST pilot trial will be included in the report of the full FAST-NAWC trial. In response to the onset of the coronavirus disease of 2019 (COVID-19) pandemic when approximately two thirds of enrollment was complete, we revised the protocol and consent form to include critically ill invasively ventilated patients with COVID-19. We also refined the statistical analysis plan (SAP) to reflect inclusion and reporting of participants with and without COVID-19. This update summarizes the changes made and their rationale and provides a refined SAP for the FAST-NAWC trial. These changes have been finalized before completion of trial follow-up and the commencement of data analysis. TRIAL REGISTRATION: Clinical Trials.gov NCT02399267.

Titration of Ventilator Settings to Target Driving Pressure and Mechanical Power.

PURPOSE: Driving pressure (ΔP) and mechanical power (MP) may be important mediators of lung injury in acute respiratory distress syndrome (ARDS) however there is little evidence for strategies directed at lowering these parameters. We applied predictive modeling to estimate the effects of modifying ventilator parameters on ΔP and MP. METHODS: 2,622 ARDS patients (Berlin criteria) from the Medical Information Mart for Intensive Care IV database (MIMIC-IV version1.0) admitted to the intensive care unit (ICU) at Beth Israel Deaconess Medical Center between 2008 and 2019 were included. Flexible confounding-adjusted regression models for time varying data were fit to estimate the effects of adjusting PEEP and tidal volume (VT) on ΔP, and adjusting VT and respiratory rate (f) on MP. RESULTS: Reduction in VT reduced ΔP and MP, with more pronounced effect on MP with lower compliance. Strategies reducing f, consistently increased MP (when VT was adjusted to maintain consistent minute ventilation). Adjustment of PEEP yielded a U-shaped effect on ΔP. CONCLUSIONS: This novel conditional modeling confirmed expected response patterns for ΔP, with the response to adjustments depending on patients' lung mechanics. Furthermore a VT -driven approach should be favored over a f -driven approach when aiming to reduce MP.

Optimal Sedation in Patients Who Receive Neuromuscular Blocking Agent Infusions for Treatment of Acute Respiratory Distress Syndrome-A Retrospective Cohort Study From a New England Health Care Network.

OBJECTIVES: Two previously published trials (ARDS et Curarisation Systematique [ACURASYS] and Reevaluation of Systemic Early Neuromuscular Blockade [ROSE]) presented equivocal evidence on the effect of neuromuscular blocking agent infusions in patients with acute respiratory distress syndrome (acute respiratory distress syndrome). The sedation regimen differed between these trials and also within the ROSE trial between treatment and control groups. We hypothesized that the proportion of deeper sedation is a mediator of the effect of neuromuscular blocking agent infusions on mortality. DESIGN: Retrospective cohort study. SETTING: Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA). PATIENTS: Intubated and mechanically ventilated ICU patients with acute respiratory distress syndrome (Berlin definition) admitted between January 2008 until June 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The proportion of deeper sedation was defined as days with nonlight sedation as a fraction of mechanical ventilation days in the ICU after acute respiratory distress syndrome diagnosis. Using clinical data obtained from a hospital network registry, 3,419 patients with acute respiratory distress syndrome were included, of whom 577 (16.9%) were treated with neuromuscular blocking agent infusions, for a mean (sd) duration of 1.8 (±1.9) days. The duration of deeper sedation was prolonged in patients receiving neuromuscular blocking agent infusions (4.6 ± 2.2 d) compared with patients without neuromuscular blocking agent infusions (2.4 ± 2.2 d; p < 0.001). The proportion of deeper sedation completely mediated the negative effect of neuromuscular blocking agent infusions on in-hospital mortality (p < 0.001). Exploratory analysis in patients who received deeper sedation revealed a beneficial effect of neuromuscular blocking agent infusions on mortality (49% vs 51%; adjusted odds ratio, 0.80; 95% CI, 0.63-0.99, adjusted absolute risk difference, -0.05; p = 0.048). CONCLUSIONS: In acute respiratory distress syndrome patients who receive neuromuscular blocking agent infusions, a prolonged, high proportion of deeper sedation is associated with increased mortality. Our data support the view that clinicians should minimize the duration of deeper sedation after recovery from neuromuscular blocking agent infusion.