The Association Between Frailty, Pao 2/Fio 2 Ratio, and Hospital Mortality: A Retrospective Registry-Based Cohort Study

OBJECTIVES: While research into critically ill patients with acute hypoxemic respiratory failure (AHRF) is growing, how this interacts with frailty is currently unknown. DESIGN: A retrospective multicentric registry-based observational study using the Australia New Zealand Intensive Care Society Adult Patient Database. SETTING AND PATIENTS: All adult (≥ 16 yr) patients admitted to 191 ICUs from January 1, 2017, to March 31, 2023, with an arterial blood gas sample within the first 24 hours were included. We categorized patients as having no AHRF (Pa o2 /F io2 ≥ 300), mild AHRF (Pa o2 /F io2 200-300), moderate AHRF (Pa o2 /F io2 100-200), and severe AHRF (Pa o2 /F io2 < 100). We defined frailty as a Clinical Frailty Scale (CFS) greater than or equal to 5. INTERVENTIONS: None. MAIN OUTCOMES: The primary outcome was in-hospital mortality. MEASUREMENTS AND MAIN RESULTS: We evaluated the association between Pa o2 /F io2 ratio and risk-adjusted mortality using restricted cubic splines with four knots. We conducted predefined subgroup analyses based on age (< 65 vs. ≥ 65 yr), mechanical ventilation status, and patients who survived ICU discharge. We included 497,185 patients; 97,317 had frailty (19.6%). AHRF was more common in patients with frailty compared with those without frailty (58.3% vs. 49.0%). Overall, 7.4% of patients died in hospital (36,791/497,185); a higher proportion were frail (16.4% vs. 5.2%). Mortality rates in patients with frailty with AHRF rose alongside worsening AHRF showing increasing absolute differences in in-hospital mortality as AHRF severity increased. Additionally, within each CFS category, increasing CFS scores also correlated with higher absolute differences in mortality. After adjusting for confounders, there was a nonlinear relationship between frailty, Pa o2 /F io2 , and in-hospital mortality, with a clear separation between each of the CFS categories. CONCLUSIONS: This multicenter, retrospective study that investigated the association between frailty, AHRF, and in-hospital mortality found that AHRF was highly prevalent in patients with frailty. Increasing frailty was associated with higher in-hospital mortality in AHRF and its increasing severity, with a nonlinear relationship.