Rapid Resolution of Hypoxemia is Common and Associated with Lower Mortality Among Intubated Patients with Acute Hypoxemic Respiratory Failure

Objective To evaluate the prevalence, clinical trajectory, and biologic phenotype of patients with rapidly improving acute hypoxemic respiratory failure (riAHRF), a subgroup of mechanically ventilated patients hypothesized to share features with the low-mortality, hypo-inflammatory phenotype previously described in rapidly improving ARDS. Design Single-center retrospective cohort study with nested biomarker analysis. Setting Academic quaternary care medical intensive care unit (ICU) in California. Patients Two cohorts of mechanically ventilated ICU patients with AHRF were included: (1) 631 patients identified through the electronic health record (EHR) between March 1, 2022 and February 1, 2024, and (2) 164 patients in the Stanford ICU Biobank who had banked plasma samples collected within 24 h of intubation. Patients with cardiogenic or traumatic etiologies were excluded in both cohorts. AHRF was defined by PaO 2 /FiO 2 < 300 or SpO 2 /FiO 2 < 315 on the day of intubation. Resolution of hypoxemia was defined by achievement of minimal ventilator settings (FiO 2 ≤ 0.4 and PEEP ≤ 5 cmH 2 O for ≥ 6 h). riAHRF was defined as reaching minimal ventilator settings within 24 h of intubation. Interventions None. Measurements and Main Results In the EHR cohort, 61% of patients experienced riAHRF. These patients had significantly lower 90-day mortality (22% vs 49%, P < .001) and more ventilator-free days (median 25 vs 23, P < .001) compared to non-riAHRF patients. Differences in clinical variables related to respiratory status, including S:F, respiratory rate, and blood gas data were subtle but statistically significant. In the BioBank cohort, riAHRF patients had lower levels of IL-8, IL-6, and sTNFR. Conclusions Rapidly improving AHRF (riAHRF) is common in patients intubated for AHRF and is associated with lower mortality and a hypo-inflammatory biomarker profile.