AbstractBackgroundThe Handling Oxygenation Targets in the Intensive Care Unit (HOT‐ICU) trial was a multicentre, randomised, parallel‐group trial of a lower oxygenation target (arterial partial pressure of oxygen [PaO₂] = 8 kPa) versus a higher oxygenation target (PaO₂ = 12 kPa) in adult ICU patients with acute hypoxaemic respiratory failure; the Handling Oxygenation Targets in coronavirus disease 2019 (HOT‐COVID) tested the same oxygenation targets in patients with confirmed COVID‐19. In this study, we aim to evaluate the long‐term effects of these oxygenation targets on cognitive and pulmonary function. We hypothesise that a lower oxygenation target throughout the ICU stay may result in cognitive impairment, whereas a higher oxygenation target may result in impaired pulmonary function.MethodsThis is the updated protocol and statistical analysis plan of two pre‐planned secondary outcomes, the long‐term cognitive function, and long‐term pulmonary function, in the HOT‐ICU and HOT‐COVID trials. Patients enrolled in both trials at selected Danish sites and surviving to 1 year after randomisation are eligible to participate. A Repeatable Battery for the Assessment of Neuropsychological Status score and a full‐body plethysmography, including diffusion capacity for carbon monoxide, will be obtained. The last patient is expected to be included in the spring of 2024.ConclusionThis study will provide important information on the long‐term effects of a lower versus a higher oxygenation target on long‐term cognitive and pulmonary functions in adult ICU patients with acute hypoxaemic respiratory failure.