Oxygenation Targets and Long-Term Cognitive and Pulmonary Functions in Hypoxemic Respiratory Failure: A Clinical Trial

Elena Crescioli; Thomas L Klitgaard; Jens Ø Riis; Ulla M Weinreich; Jens-Ulrik S Jensen; Stine R Vestergaard; Anne-Marie G Bunzel; Anne Sofie B Eriksen; Simon H Gudbjerg; Lone M Poulsen; Anne C Brøchner; Camilla B Mortensen; Trine Haberlandt; Christian N Meyer; Lone Braagaard; Jann Mortensen; Theis Lange; Anders Perner; Olav L Schjørring; Bodil S Rasmussen

doi:10.1164/rccm.202412-2499OC

Oxygenation Targets and Long-Term Cognitive and Pulmonary Functions in Hypoxemic Respiratory Failure: A Clinical Trial

Elena Crescioli, Thomas L Klitgaard, Jens Ø Riis, Ulla M Weinreich, Jens-Ulrik S Jensen, Stine R Vestergaard, Anne-Marie G Bunzel, Anne Sofie B Eriksen, Simon H Gudbjerg, Lone M Poulsen, Anne C Brøchner, Camilla B Mortensen, Trine Haberlandt, Christian N Meyer, Lone Braagaard, Jann Mortensen, Theis Lange, Anders Perner, Olav L Schjørring, Bodil S Rasmussen

Abstract

RATIONALE: In ICU patients, lower oxygenation targets may impair long-term cognitive function, whereas higher targets may impair long-term pulmonary function.

OBJECTIVES: We sought to assess the effects of a PaO2 target of 60 versus 90 mm Hg on 1-year cognitive and pulmonary functions in ICU survivors of acute hypoxemic respiratory failure.

METHODS: A total of 3,654 patients were randomized in the Handling Oxygenation Targets in the ICU and the Handling Oxygenation Targets in COVID-19 trials: 1,916 (52.4%) survived at 1 year, of which 1,244 (64.9%) were eligible. We assessed two preplanned 1-year outcomes: cognitive function, measured using the global score of the Repeatable Battery for the Assessment of Neuropsychological Status, and pulmonary function, evaluated as the percentage of predicted DlCO.

MEASUREMENTS AND MAIN RESULTS: A total of 417/1,244 (33.5%) eligible survivors were included, representing 11.4% of the original trial population. The Global Repeatable Battery for the Assessment of Neuropsychological Status score was obtained from 187 survivors in the lower oxygenation group (mean = 78; SD = 19) and 188 in the higher oxygenation group (mean = 76; SD = 21); adjusted mean difference = 2 (95% confidence interval = -2 to 6). DlCO was measured in 192 survivors in the lower oxygenation group (mean = 68%; SD = 22) and 195 in the higher oxygenation group (mean = 73%; SD = 25); adjusted mean difference = -5 percentage points (95% CI = -9 to -1).

CONCLUSIONS: A PaO2 target of 60 versus 90 mm Hg appeared to result in similar cognitive impairment but might reduce pulmonary diffusion capacity in ICU survivors of hypoxemic respiratory failure included in this 1-year follow-up.Clinical trial registered with www.

CLINICALTRIALS: gov (NCT03174002 and NCT04425031).

Original language	English
Journal	American Journal of Respiratory and Critical Care Medicine
Volume	212
Issue number	3
Pages (from-to)	464-473
Number of pages	10
ISSN	1073-449X
DOIs	https://doi.org/10.1164/rccm.202412-2499OC
Publication status	Published - 1 Mar 2026

Keywords

Aged
COVID-19/therapy
Cognition/physiology
Cognitive Dysfunction/etiology
Female
Humans
Hypoxia/therapy
Intensive Care Units
Male
Middle Aged
Oxygen/blood
Respiratory Function Tests
Respiratory Insufficiency/therapy

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Crescioli, E., Klitgaard, T. L., Riis, J. Ø., Weinreich, U. M., Jensen, J.-U. S., Vestergaard, S. R., Bunzel, A.-M. G., Eriksen, A. S. B., Gudbjerg, S. H., Poulsen, L. M., Brøchner, A. C., Mortensen, C. B., Haberlandt, T., Meyer, C. N., Braagaard, L., Mortensen, J., Lange, T., Perner, A., Schjørring, O. L., & Rasmussen, B. S. (2026). Oxygenation Targets and Long-Term Cognitive and Pulmonary Functions in Hypoxemic Respiratory Failure: A Clinical Trial. American Journal of Respiratory and Critical Care Medicine, 212(3), 464-473. https://doi.org/10.1164/rccm.202412-2499OC

Oxygenation Targets and Long-Term Cognitive and Pulmonary Functions in Hypoxemic Respiratory Failure: A Clinical Trial. / Crescioli, Elena; Klitgaard, Thomas L; Riis, Jens Ø et al.
In: American Journal of Respiratory and Critical Care Medicine, Vol. 212, No. 3, 01.03.2026, p. 464-473.

Research output: Contribution to journal › Journal article › Research › peer-review

Crescioli, E, Klitgaard, TL, Riis, JØ, Weinreich, UM, Jensen, J-US, Vestergaard, SR, Bunzel, A-MG, Eriksen, ASB, Gudbjerg, SH, Poulsen, LM, Brøchner, AC, Mortensen, CB, Haberlandt, T, Meyer, CN, Braagaard, L , Mortensen, J, Lange, T, Perner, A, Schjørring, OL & Rasmussen, BS 2026, 'Oxygenation Targets and Long-Term Cognitive and Pulmonary Functions in Hypoxemic Respiratory Failure: A Clinical Trial', American Journal of Respiratory and Critical Care Medicine, vol. 212, no. 3, pp. 464-473. https://doi.org/10.1164/rccm.202412-2499OC

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title = "Oxygenation Targets and Long-Term Cognitive and Pulmonary Functions in Hypoxemic Respiratory Failure: A Clinical Trial",

abstract = "RATIONALE: In ICU patients, lower oxygenation targets may impair long-term cognitive function, whereas higher targets may impair long-term pulmonary function.OBJECTIVES: We sought to assess the effects of a PaO2 target of 60 versus 90 mm Hg on 1-year cognitive and pulmonary functions in ICU survivors of acute hypoxemic respiratory failure.METHODS: A total of 3,654 patients were randomized in the Handling Oxygenation Targets in the ICU and the Handling Oxygenation Targets in COVID-19 trials: 1,916 (52.4\%) survived at 1 year, of which 1,244 (64.9\%) were eligible. We assessed two preplanned 1-year outcomes: cognitive function, measured using the global score of the Repeatable Battery for the Assessment of Neuropsychological Status, and pulmonary function, evaluated as the percentage of predicted DlCO.MEASUREMENTS AND MAIN RESULTS: A total of 417/1,244 (33.5\%) eligible survivors were included, representing 11.4\% of the original trial population. The Global Repeatable Battery for the Assessment of Neuropsychological Status score was obtained from 187 survivors in the lower oxygenation group (mean = 78; SD = 19) and 188 in the higher oxygenation group (mean = 76; SD = 21); adjusted mean difference = 2 (95\% confidence interval = -2 to 6). DlCO was measured in 192 survivors in the lower oxygenation group (mean = 68\%; SD = 22) and 195 in the higher oxygenation group (mean = 73\%; SD = 25); adjusted mean difference = -5 percentage points (95\% CI = -9 to -1).CONCLUSIONS: A PaO2 target of 60 versus 90 mm Hg appeared to result in similar cognitive impairment but might reduce pulmonary diffusion capacity in ICU survivors of hypoxemic respiratory failure included in this 1-year follow-up.Clinical trial registered with www.CLINICALTRIALS: gov (NCT03174002 and NCT04425031).",

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author = "Elena Crescioli and Klitgaard, \{Thomas L\} and Riis, \{Jens {\O}\} and Weinreich, \{Ulla M\} and Jensen, \{Jens-Ulrik S\} and Vestergaard, \{Stine R\} and Bunzel, \{Anne-Marie G\} and Eriksen, \{Anne Sofie B\} and Gudbjerg, \{Simon H\} and Poulsen, \{Lone M\} and Br{\o}chner, \{Anne C\} and Mortensen, \{Camilla B\} and Trine Haberlandt and Meyer, \{Christian N\} and Lone Braagaard and Jann Mortensen and Theis Lange and Anders Perner and Schj{\o}rring, \{Olav L\} and Rasmussen, \{Bodil S\}",

year = "2026",

month = mar,

day = "1",

doi = "10.1164/rccm.202412-2499OC",

language = "English",

volume = "212",

pages = "464--473",

journal = "American Journal of Respiratory and Critical Care Medicine",

issn = "1073-449X",

publisher = "American Thoracic Society",

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TY - JOUR

T1 - Oxygenation Targets and Long-Term Cognitive and Pulmonary Functions in Hypoxemic Respiratory Failure

T2 - A Clinical Trial

AU - Crescioli, Elena

AU - Klitgaard, Thomas L

AU - Riis, Jens Ø

AU - Weinreich, Ulla M

AU - Jensen, Jens-Ulrik S

AU - Vestergaard, Stine R

AU - Bunzel, Anne-Marie G

AU - Eriksen, Anne Sofie B

AU - Gudbjerg, Simon H

AU - Poulsen, Lone M

AU - Brøchner, Anne C

AU - Mortensen, Camilla B

AU - Haberlandt, Trine

AU - Meyer, Christian N

AU - Braagaard, Lone

AU - Mortensen, Jann

AU - Lange, Theis

AU - Perner, Anders

AU - Schjørring, Olav L

AU - Rasmussen, Bodil S

PY - 2026/3/1

Y1 - 2026/3/1

N2 - RATIONALE: In ICU patients, lower oxygenation targets may impair long-term cognitive function, whereas higher targets may impair long-term pulmonary function.OBJECTIVES: We sought to assess the effects of a PaO2 target of 60 versus 90 mm Hg on 1-year cognitive and pulmonary functions in ICU survivors of acute hypoxemic respiratory failure.METHODS: A total of 3,654 patients were randomized in the Handling Oxygenation Targets in the ICU and the Handling Oxygenation Targets in COVID-19 trials: 1,916 (52.4%) survived at 1 year, of which 1,244 (64.9%) were eligible. We assessed two preplanned 1-year outcomes: cognitive function, measured using the global score of the Repeatable Battery for the Assessment of Neuropsychological Status, and pulmonary function, evaluated as the percentage of predicted DlCO.MEASUREMENTS AND MAIN RESULTS: A total of 417/1,244 (33.5%) eligible survivors were included, representing 11.4% of the original trial population. The Global Repeatable Battery for the Assessment of Neuropsychological Status score was obtained from 187 survivors in the lower oxygenation group (mean = 78; SD = 19) and 188 in the higher oxygenation group (mean = 76; SD = 21); adjusted mean difference = 2 (95% confidence interval = -2 to 6). DlCO was measured in 192 survivors in the lower oxygenation group (mean = 68%; SD = 22) and 195 in the higher oxygenation group (mean = 73%; SD = 25); adjusted mean difference = -5 percentage points (95% CI = -9 to -1).CONCLUSIONS: A PaO2 target of 60 versus 90 mm Hg appeared to result in similar cognitive impairment but might reduce pulmonary diffusion capacity in ICU survivors of hypoxemic respiratory failure included in this 1-year follow-up.Clinical trial registered with www.CLINICALTRIALS: gov (NCT03174002 and NCT04425031).

AB - RATIONALE: In ICU patients, lower oxygenation targets may impair long-term cognitive function, whereas higher targets may impair long-term pulmonary function.OBJECTIVES: We sought to assess the effects of a PaO2 target of 60 versus 90 mm Hg on 1-year cognitive and pulmonary functions in ICU survivors of acute hypoxemic respiratory failure.METHODS: A total of 3,654 patients were randomized in the Handling Oxygenation Targets in the ICU and the Handling Oxygenation Targets in COVID-19 trials: 1,916 (52.4%) survived at 1 year, of which 1,244 (64.9%) were eligible. We assessed two preplanned 1-year outcomes: cognitive function, measured using the global score of the Repeatable Battery for the Assessment of Neuropsychological Status, and pulmonary function, evaluated as the percentage of predicted DlCO.MEASUREMENTS AND MAIN RESULTS: A total of 417/1,244 (33.5%) eligible survivors were included, representing 11.4% of the original trial population. The Global Repeatable Battery for the Assessment of Neuropsychological Status score was obtained from 187 survivors in the lower oxygenation group (mean = 78; SD = 19) and 188 in the higher oxygenation group (mean = 76; SD = 21); adjusted mean difference = 2 (95% confidence interval = -2 to 6). DlCO was measured in 192 survivors in the lower oxygenation group (mean = 68%; SD = 22) and 195 in the higher oxygenation group (mean = 73%; SD = 25); adjusted mean difference = -5 percentage points (95% CI = -9 to -1).CONCLUSIONS: A PaO2 target of 60 versus 90 mm Hg appeared to result in similar cognitive impairment but might reduce pulmonary diffusion capacity in ICU survivors of hypoxemic respiratory failure included in this 1-year follow-up.Clinical trial registered with www.CLINICALTRIALS: gov (NCT03174002 and NCT04425031).

KW - Aged

KW - COVID-19/therapy

KW - Cognition/physiology

KW - Cognitive Dysfunction/etiology

KW - Female

KW - Humans

KW - Hypoxia/therapy

KW - Intensive Care Units

KW - Male

KW - Middle Aged

KW - Oxygen/blood

KW - Respiratory Function Tests

KW - Respiratory Insufficiency/therapy

U2 - 10.1164/rccm.202412-2499OC

DO - 10.1164/rccm.202412-2499OC

M3 - Journal article

C2 - 40920961

SN - 1073-449X

VL - 212

SP - 464

EP - 473

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

IS - 3

ER -

Oxygenation Targets and Long-Term Cognitive and Pulmonary Functions in Hypoxemic Respiratory Failure: A Clinical Trial

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Keywords

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