Background Delirium during acute respiratory failure is common and morbid. Pharmacologic sedation is a major risk factor for delirium, but some sedation is often necessary for the provision of safe care of mechanically ventilated patients. A simple, transparent model that predicts sedative-associated delirium in mechanically ventilated ICU patients could be used to guide decisions about personalized sedation.

Research Question Can the risk of sedative-associated delirium be estimated in mechanically-ventilated ICU patients?

Study Design and Methods Using the subset of patients in a previously-published ICU cohort who received mechanical ventilation, we performed backward stepwise logistic regression to derive a model predictive of sedative-associated delirium. We validated this model internally using hundredfold bootstrapping. We then validated this model externally in a separate prospective cohort of mechanically ventilated ICU patients.

Results 836 patients comprised the derivation cohort. Backwards stepwise regression produced a model with age, BMI, sepsis, SOFA, malignancy, COPD, stroke, sex, and doses of sedatives (opioids, propofol, and/or benzodiazepines) as predictors of sedative-associated delirium. The model had very good discriminative power, with an area under the receiver-operator curve (AUROC) of 0.83. Internal validation via bootstrapping showed preserved discriminatory function with an AUROC of 0.81 and graphical evidence of good calibration. External validation in a separate set of 340 patients showed good discrimination, with AUROC of 0.70.

Interpretation Sedative-associated delirium during acute respiratory failure requiring mechanical ventilation can be predicted using a simple, transparent model, which can now be validated in a prospective study.

Competing interests: NTP, CAO, KMP, and CAF declare that they have no competing interests. GDK has received research funding from Genentech, Inc, and Pfizer, Inc, unrelated to this work. BJM receives research funding from Genentech, and previously served as consultant or advisory board member for BioAegis, Synairgen Research Ltd, and Boehringer Ingelheim. PPP declares no competing interest. EWE reports honoraria for continuing medical education lectures sponsored by Pfizer, and study support (investigational drug provision, no direct payments) from Eli Lilly. TDG receives research funding from Ceribell and served previously on an advisory board for Lungpacer Medical Inc.

Funding: This work was supported by NIH grants F32HL158058 (to NTP), R03HL162655 (to GDK), P01HL114453 (to BJM), and R01AG027472 (to EWE) and by a Merit Review Grant from Department of Veterans Affairs (to EWE).

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Ethics approval and consent to participate: BRAIN-ICU and MIND-ICU were approved by the institutional review board (IRB) at Vanderbilt University, and by local IRBs at each site, when the study was initially approved. The use of the data was approved by the IRB at the University of Pittsburgh as PRO18020380. The ALIR was approved as STUDY19050099 by the IRB at the University of Pittsburgh. Both studies involve(d) consent by the patient or his/her legally authorized representative.

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Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.