Hallie C Prescott, Michael W Sjoding, Kenneth M Langa, Theodore J Iwashyna, Daniel F McAuley

Acute hypoxic respiratory failure (AHRF) is associated with significant acute mortality. It is unclear whether later mortality is predominantly driven by pre-existing comorbid disease, the acute inciting event or is the result of AHRF itself. Observational cohort study of elderly US Health and Retirement Study (HRS) participants in fee-for-service Medicare (1998-2012). Patients hospitalised with AHRF were matched 1:1 to otherwise similar adults who were not currently hospitalised and separately to patients hospitalised with acute inciting events (pneumonia, non-pulmonary infection, aspiration, trauma, pancreatitis) that may result in AHRF, here termed at-risk hospitalisations. The primary outcome was late mortality-death in the 31 days to 2 years following hospital admission. Among 15 075 HRS participants, we identified 1268 AHRF and 13 117 at-risk hospitalisations. AHRF hospitalisations were matched to 1157 non-hospitalised adults and 1017 at-risk hospitalisations. Among patients who survived at least 30 days, AHRF was associated with a 24.4% (95%CI 19.9% to 28.9%, p<0.001) absolute increase in late mortality relative to adults not currently hospitalised and a 6.7% (95%CI 1.7% to 11.7%, p=0.01) increase relative to adults hospitalised with acute inciting event(s) alone. At-risk hospitalisation explained 71.2% of the increased odds of late mortality, whereas the development of AHRF itself explained 28.8%. Risk for death was equivalent to at-risk hospitalisation beyond 90 days, but remained elevated for more than 1 year compared with non-hospitalised controls. In this national sample of older Americans, approximately one in four survivors with AHRF had a late death not explained by pre-AHRF health status. More than 70% of this increased risk was associated with hospitalisation for acute inciting events, while 30% was associated with hypoxemic respiratory failure.