Predicting Time to Death After Withdrawal of Life-Sustaining Measures Using Vital Sign Variability: Derivation and Validation

To develop a predictive model using vital sign (heart rate and arterial blood pressure) variability to predict time to death after withdrawal of life-supporting measures. DESIGN: Retrospective analysis of observational data prospectively collected as part of the Death Prediction and Physiology after Removal of Therapy study between May 1, 2014, and May 1, 2018. SETTING: Adult ICU. PATIENTS: Adult patients in the ICU with a planned withdrawal of life-supporting measures and an expectation of imminent death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Vital sign waveforms and clinical data were prospectively collected from 429 patients enrolled from 20 ICUs across Canada, the Czech Republic, and the Netherlands. Vital sign variability metrics were calculated during the hour prior to withdrawal. Patients were randomly assigned to the derivation cohort (288 patients) or the validation cohort (141 patients), of which 103 and 54, respectively, were eligible for organ donation after circulatory death. Random survival forest models were developed to predict the probability of death within 30, 60, and 120 minutes following withdrawal using variability metrics, features from existing clinical models, and/or the physician’s prediction of rapid death. A model employing variability metrics alone performed similarly to a model employing clinical features, whereas the combination of variability, clinical features, and physician’s prediction achieved the highest area under the receiver operating characteristics curve of all models at 0.78 (0.7–0.86), 0.79 (0.71–0.87), and 0.8 (0.72–0.88) for 30-, 60- and 120-minute predictions, respectively. CONCLUSIONS: Machine learning models of vital sign variability data before withdrawal of life-sustaining measures, combined with clinical features and the physician’s prediction, are useful to predict time to death. The impact of providing this information for decision support for organ donation merits further investigation.