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Background: Early prediction model of hemodynamic instability has the potential to improve the critical care, whereas limited external validation on the generalizability. We aimed to independently validate the Hemodynamic Stability Index (HSI), a multi-parameter machine learning model, in predicting hemodynamic instability in Asian patients., Method: Hemodynamic instability was marked by using inotropic, vasopressor, significant fluid therapy, and/or blood transfusions. This retrospective study included among 15,967 ICU patients who aged 20 years or older (not included 20 years) and stayed in ICU for more than 6 h admitted to Taipei Veteran General Hospital (TPEVGH) between January 1, 2010, and March 31, 2020, of whom hemodynamic instability occurred in 3053 patients (prevalence = 19%). These patients in unstable group received at least one intervention during their ICU stays, and the HSI score of both stable and unstable group was calculated in every hour before intervention. The model performance was assessed using the area under the receiver operating characteristic curve (AUROC) and was compared to single indicators like systolic blood pressure (SBP) and shock index. The hemodynamic instability alarm was set by selecting optimal threshold with high sensitivity, acceptable specificity, and lead time before intervention was calculated to indicate when patients were firstly identified as high risk of hemodynamic instability., Results: The AUROC of HSI was 0.76 (95% CI, 0.75-0.77), which performed significantly better than shock Index (0.7; 95% CI, 0.69-0.71) and SBP (0.69; 95% CI, 0.68-0.70). By selecting 0.7 as a threshold, HSI predicted 72% of all 3053 patients who received hemodynamic interventions with 67% in specificity. Time-varying results also showed that HSI score significantly outperformed single indicators even up to 24 h before intervention. And 95% unstable patients can be identified more than 5 h in advance., Conclusions: The HSI has acceptable discrimination but underestimates the risk of stable patients in predicting the onset of hemodynamic instability in an external cohort., (© 2022. The Author(s).)