BACKGROUND: The study of the inclusion of new variables in already existing early warning scores is a growing field. The aim of this work was to determine how capnometry measurements, in the form of end-tidal CO2 (ETCO2) and the perfusion index (PI), could improve the National Early Warning Score (NEWS2). METHODS: A secondary, prospective, multicenter, cohort study was undertaken in adult patients with unselected acute diseases who needed continuous monitoring in the emergency department (ED), involving two tertiary hospitals in Spain from October 1, 2022, to June 30, 2023. The primary outcome was 30-day all-cause in-hospital mortality. Demographics and vital signs necessary for NEWS2, ETCO2 and PI were collected. RESULTS: A total of 687 patients were included in the study. The median age was 79 years (IQR: 69-86), and 36.7 % were females, with an in-hospital mortality rate of 6.7 %. The NEWS2 score was 7 points for nonsurvivors and 4 points for survivors (p <
0.001). The EtCO2 levels were 30 mmHg (26-35) and 23 mmHg (16-30), and the PI levels were 4.7% (2.2-8.1) and 2.5 % (0.98-4.4) for survivors and nonsurvivors, respectively (both p <
0.001). The discrimination capacity of NEWS2 was AUC = 0.769 (95 % CI: 0.707-0.831), that of EtCO2 + PI was AUC = 0.737 (95 % CI: 0.66-0.814), and that of NEWS2 + ETCO2 + PI was AUC = 0.804 (95 % CI: 0.745-0.863). CONCLUSIONS: The present study findings indicate that the PI and ETCO2 improved the ability of the NEWS2 to predict 30-day in-hospital mortality. The novel association of the NEWS2 with the PI and ETCO2 should be considered since it could improve the identification of patients at risk of clinical worsening.