Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure

doi:10.1056/NEJMoa2032510

Randomized Controlled Trial

. 2021 Apr 8;384(14):1301-1311.

doi: 10.1056/NEJMoa2032510. Epub 2021 Jan 20.

Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure

Olav L Schjørring¹, Thomas L Klitgaard¹, Anders Perner¹, Jørn Wetterslev¹, Theis Lange¹, Martin Siegemund¹, Minna Bäcklund¹, Frederik Keus¹, Jon H Laake¹, Matthew Morgan¹, Katrin M Thormar¹, Søren A Rosborg¹, Jannie Bisgaard¹, Annette E S Erntgaard¹, Anne-Sofie H Lynnerup¹, Rasmus L Pedersen¹, Elena Crescioli¹, Theis C Gielstrup¹, Meike T Behzadi¹, Lone M Poulsen¹, Stine Estrup¹, Jens P Laigaard¹, Cheme Andersen¹, Camilla B Mortensen¹, Björn A Brand¹, Jonathan White¹, Inge-Lise Jarnvig¹, Morten H Møller¹, Lars Quist¹, Morten H Bestle¹, Martin Schønemann-Lund¹, Maj K Kamper¹, Mathias Hindborg¹, Alexa Hollinger¹, Caroline E Gebhard¹, Núria Zellweger¹, Christian S Meyhoff¹, Mathias Hjort¹, Laura K Bech¹, Thorbjørn Grøfte¹, Helle Bundgaard¹, Lars H M Østergaard¹, Maria A Thyø¹, Thomas Hildebrandt¹, Bülent Uslu¹, Christoffer G Sølling¹, Nette Møller-Nielsen¹, Anne C Brøchner¹, Morten Borup¹, Marjatta Okkonen¹, Willem Dieperink¹, Ulf G Pedersen¹, Anne S Andreasen¹, Lone Buus¹, Tayyba N Aslam¹, Robert R Winding¹, Joerg C Schefold¹, Stine B Thorup¹, Susanne A Iversen¹, Janus Engstrøm¹, Maj-Brit N Kjær¹, Bodil S Rasmussen¹; HOT-ICU Investigators

Collaborators, Affiliations

Collaborators

HOT-ICU Investigators:
B S Rasmussen, M Bäcklund, F Keus, T L Klitgaard, J H Laake, T Lange, M Morgan, A Perner, O L Schjørring, M Siegemund, K M Thormar, J Wetterslev, D De Backer, J-F Timsit, A K Jensen, S R Aagaard, M T Behzadi, A S B Eriksen, A-M G Bunzel, K Jensen, N M Jensen, T Jørgensen, M Levin, R Moulvad, H A Mouritsen, L S Søndergaard, S R Vestergaard, L M Poulsen, V Khridin, C B Mortensen, J P Laigaard, C Andersen, S Estrup, N Andersen-Ranberg, L Nebrich, J V Jensen, H C Boesen, M H Møller, B A Brand, L Russell, M N Kjær, G K Vesterlund, J F Degn, K R Uhre, A L S Lindgaard, T S Meyhoff, M Wetterslev, M W Petersen, K L Ellekjær, M O Collet, B Westergaard, C O Steensen, J Wiis, M Winther-Olesen, S T Sigurdsson, M H Bestle, M Schønemann-Lund, M K Kamper, S Lauritzen, L Valbjørn, B Christensen, J G Hansen, K J Nielsen, B Thaarslund, C S Skandov, T S Galle, M Ibsen, L Hein, T U Skram, D F Christensen, M Østergaard, N Wesche, J Meisner, A Hollinger, C Gebhard, N Zellweger, D Knobel, A Zaiser, P-L Siegemund, T Zehnder, Y Bovey, A Blum, S Reinhold, C S Meyhoff, M Hjort, L K Bech, D B Jensen, K M Sørensen, P S Rasmussen, A R Hjortdal, N Reiter, N E Clausen, T Grøfte, M Rostgaard-Knudsen, M Vang, H Bundgaard, D F Jensen, L H M Østergaard, M A Thyø, M B Nielsen, T Elkmann, T Hildebrandt, B Uslu, C G Sølling, N Møller-Nielsen, S K Pedersen, K K Knudsen, L Liboriussen, A C Brøchner, T N Haberlandt, L S Nielsen, M Borup, C F Elvander, N H Bæk, K E Fabirkiewicz, S H Lundorff, J S Nielsen, M Pedersen, J S Knudsen, W Dieperink, H Franke, H Kranen, M Kreijtz, J Wieringa, M Onrust, E van den Berg, U G Pedersen, K T Kristiansen, J Christensen, M Okkonen, M Valkonen, E Lappi, S Sutinen, L Pettilä, T Suhonen, J Heinonen, A S Andreasen, H Christensen, K Skovmand, H Brix, H Knudsen, L Buus, D Due-Rasmussen, T N Aslam, R Winding, N Dey, R L Læbel, T B Jensen, R Mærkedahl, A H S Nielsen, L E F Mahler, B G Curtz, S Haubjerg, J C Schefold, C A Pfortmueller, J Aeby, D Bertschi, M Schilling, F Stoehr, M Jong, D Zacharias, M Roth, L Fazlija, M Akaltan, H-H Bülow, S B Thorup, A A Aaen, S A Iversen, H H Sørensen, H B Pedersen, J Brushøj, N Foldager, K Marcussen, J Karttunen, I Parviainen, A Uusaro, S Bendel, M Lång, N Julkunen, T Nyyssönen, M Reinikainen, V Koskela, S Rahikainen, E Vaskelainen, E Halonen, S Julkunen, S Rissanen, A Williams, E Thomas, H Hill, J Brooks, J Cole, M Davies, R Davies, M Wise, A Ciubotariu, M Pawlowicz-Dworzanska, K A Damgaard, M Kruse, Z Ali, D Brønnum, L Midtgaard, R M Andersen, L N Hansen, M Sharman, A Sukumaran, R Quayle, E Connaughton, R Clark, K Wylie, J Bannard-Smith, K Birchall, F Pomeroy, H M Betsch, L S Johansen, N K Schønemann, A Pulkkinen, R Laru-Sompa, S Tolmunen, J Hartikainen, C Lynch, L Jones, B Deacon, L Roche, K Turner, J Grönlund, R Takala, J Heiro, M Järvisalo, W Siirala, O Inkinen, M Valtonen, O Arola, R Laitio, J Kauppinen, S Kentala, E Loikas, P Haltia, A Joseph, A Swain, R Burden, M Grout, T O'Brien, L Balshaw, M Danha, A Jose, S Jones, E Morino, L Mumelj, M I Sigurdsson, O Hoiting, M Peters, E Rengers, A Prinssen, M Evers, P D G Alexander, L Ward, C Bowyer, A Walden, N Jacques, P Bhachu

Affiliation

¹ From the Department of Anesthesia and Intensive Care, Aalborg University Hospital, Aalborg University, Aalborg (O.L.S., T.L.K., S.A.R., J.B., A.E.S.E., A.-S.H.L., R.L.P., E.C., T.C.G., M.T.B., B.S.R.), Zealand University Hospital, Køge (L.M.P., S.E., J.P.L., C.A., C.B.M.), Rigshospitalet (A.P., B.A.B., J. Wetterslev, I.-L.J., M.H.M., L.Q., M.-B.N.K.) and the Section of Biostatistics, Department of Public Health (T.L.), University of Copenhagen, Bispebjerg, and Frederiksberg Hospital (C.S.M., M. Hjort, L.K.B.) and the Copenhagen Trial Unit (J. White, J.E.), Copenhagen, Nordsjaellands Hospital, Hillerod (M.H.B., M.S.-L., M.K.K., M. Hindborg), Randers Hospital, Randers (T.G., H.B.), Aarhus University Hospital, Skejby North, Aarhus (L.H.M.Ø., M.A.T.), Zealand University Hospital, Roskilde (T.H., B.U.), Viborg Hospital, Viborg (C.G.S., N.M.-N.), Kolding Hospital, Kolding (A.C.B., M. Bäcklund), Hvidovre Hospital, Hvidovre (U.G.P.), Herlev Hospital, Herlev (A.S.A.), Horsens Hospital, Horsens (L.B.), Herning Hospital, Herning (R.R.W.), Holbæk Hospital, Holbæk (S.B.T.), and Slagelse Hospital, Slagelse (S.A.I.) - all in Denmark; the Department of Intensive Care and Department of Clinical Research, University of Basel, Basel (M.S., A.H., C.E.G., N.Z.), and the Department of Intensive Care, Inselspital, University of Bern, Bern (J.C.S.) - both in Switzerland; the Department of Perioperative, Intensive Care and Pain Medicine, Helsinki University Hospital, Helsinki (M.B., M.O.); the Department of Critical Care, University Medical Center Groningen, Groningen, the Netherlands (F.K., W.D.); the Departments of Anesthesia and Intensive Care and of Clinical Research, Rikshospitalet, Oslo University Hospital, Oslo (J.H.L., T.N.A.); the Department of Intensive Care, Cardiff University Hospital of Wales, Cardiff, United Kingdom (M.M.); and the Department of Anesthesia and Intensive Care, Landspitali University Hospital, Reykjavik, Iceland (K.M.T.).

PMID: 33471452
DOI: 10.1056/NEJMoa2032510

Randomized Controlled Trial

Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure

Olav L Schjørring et al. N Engl J Med. 2021.

. 2021 Apr 8;384(14):1301-1311.

doi: 10.1056/NEJMoa2032510. Epub 2021 Jan 20.

Authors

Collaborators

HOT-ICU Investigators:
B S Rasmussen, M Bäcklund, F Keus, T L Klitgaard, J H Laake, T Lange, M Morgan, A Perner, O L Schjørring, M Siegemund, K M Thormar, J Wetterslev, D De Backer, J-F Timsit, A K Jensen, S R Aagaard, M T Behzadi, A S B Eriksen, A-M G Bunzel, K Jensen, N M Jensen, T Jørgensen, M Levin, R Moulvad, H A Mouritsen, L S Søndergaard, S R Vestergaard, L M Poulsen, V Khridin, C B Mortensen, J P Laigaard, C Andersen, S Estrup, N Andersen-Ranberg, L Nebrich, J V Jensen, H C Boesen, M H Møller, B A Brand, L Russell, M N Kjær, G K Vesterlund, J F Degn, K R Uhre, A L S Lindgaard, T S Meyhoff, M Wetterslev, M W Petersen, K L Ellekjær, M O Collet, B Westergaard, C O Steensen, J Wiis, M Winther-Olesen, S T Sigurdsson, M H Bestle, M Schønemann-Lund, M K Kamper, S Lauritzen, L Valbjørn, B Christensen, J G Hansen, K J Nielsen, B Thaarslund, C S Skandov, T S Galle, M Ibsen, L Hein, T U Skram, D F Christensen, M Østergaard, N Wesche, J Meisner, A Hollinger, C Gebhard, N Zellweger, D Knobel, A Zaiser, P-L Siegemund, T Zehnder, Y Bovey, A Blum, S Reinhold, C S Meyhoff, M Hjort, L K Bech, D B Jensen, K M Sørensen, P S Rasmussen, A R Hjortdal, N Reiter, N E Clausen, T Grøfte, M Rostgaard-Knudsen, M Vang, H Bundgaard, D F Jensen, L H M Østergaard, M A Thyø, M B Nielsen, T Elkmann, T Hildebrandt, B Uslu, C G Sølling, N Møller-Nielsen, S K Pedersen, K K Knudsen, L Liboriussen, A C Brøchner, T N Haberlandt, L S Nielsen, M Borup, C F Elvander, N H Bæk, K E Fabirkiewicz, S H Lundorff, J S Nielsen, M Pedersen, J S Knudsen, W Dieperink, H Franke, H Kranen, M Kreijtz, J Wieringa, M Onrust, E van den Berg, U G Pedersen, K T Kristiansen, J Christensen, M Okkonen, M Valkonen, E Lappi, S Sutinen, L Pettilä, T Suhonen, J Heinonen, A S Andreasen, H Christensen, K Skovmand, H Brix, H Knudsen, L Buus, D Due-Rasmussen, T N Aslam, R Winding, N Dey, R L Læbel, T B Jensen, R Mærkedahl, A H S Nielsen, L E F Mahler, B G Curtz, S Haubjerg, J C Schefold, C A Pfortmueller, J Aeby, D Bertschi, M Schilling, F Stoehr, M Jong, D Zacharias, M Roth, L Fazlija, M Akaltan, H-H Bülow, S B Thorup, A A Aaen, S A Iversen, H H Sørensen, H B Pedersen, J Brushøj, N Foldager, K Marcussen, J Karttunen, I Parviainen, A Uusaro, S Bendel, M Lång, N Julkunen, T Nyyssönen, M Reinikainen, V Koskela, S Rahikainen, E Vaskelainen, E Halonen, S Julkunen, S Rissanen, A Williams, E Thomas, H Hill, J Brooks, J Cole, M Davies, R Davies, M Wise, A Ciubotariu, M Pawlowicz-Dworzanska, K A Damgaard, M Kruse, Z Ali, D Brønnum, L Midtgaard, R M Andersen, L N Hansen, M Sharman, A Sukumaran, R Quayle, E Connaughton, R Clark, K Wylie, J Bannard-Smith, K Birchall, F Pomeroy, H M Betsch, L S Johansen, N K Schønemann, A Pulkkinen, R Laru-Sompa, S Tolmunen, J Hartikainen, C Lynch, L Jones, B Deacon, L Roche, K Turner, J Grönlund, R Takala, J Heiro, M Järvisalo, W Siirala, O Inkinen, M Valtonen, O Arola, R Laitio, J Kauppinen, S Kentala, E Loikas, P Haltia, A Joseph, A Swain, R Burden, M Grout, T O'Brien, L Balshaw, M Danha, A Jose, S Jones, E Morino, L Mumelj, M I Sigurdsson, O Hoiting, M Peters, E Rengers, A Prinssen, M Evers, P D G Alexander, L Ward, C Bowyer, A Walden, N Jacques, P Bhachu

Affiliation

¹ From the Department of Anesthesia and Intensive Care, Aalborg University Hospital, Aalborg University, Aalborg (O.L.S., T.L.K., S.A.R., J.B., A.E.S.E., A.-S.H.L., R.L.P., E.C., T.C.G., M.T.B., B.S.R.), Zealand University Hospital, Køge (L.M.P., S.E., J.P.L., C.A., C.B.M.), Rigshospitalet (A.P., B.A.B., J. Wetterslev, I.-L.J., M.H.M., L.Q., M.-B.N.K.) and the Section of Biostatistics, Department of Public Health (T.L.), University of Copenhagen, Bispebjerg, and Frederiksberg Hospital (C.S.M., M. Hjort, L.K.B.) and the Copenhagen Trial Unit (J. White, J.E.), Copenhagen, Nordsjaellands Hospital, Hillerod (M.H.B., M.S.-L., M.K.K., M. Hindborg), Randers Hospital, Randers (T.G., H.B.), Aarhus University Hospital, Skejby North, Aarhus (L.H.M.Ø., M.A.T.), Zealand University Hospital, Roskilde (T.H., B.U.), Viborg Hospital, Viborg (C.G.S., N.M.-N.), Kolding Hospital, Kolding (A.C.B., M. Bäcklund), Hvidovre Hospital, Hvidovre (U.G.P.), Herlev Hospital, Herlev (A.S.A.), Horsens Hospital, Horsens (L.B.), Herning Hospital, Herning (R.R.W.), Holbæk Hospital, Holbæk (S.B.T.), and Slagelse Hospital, Slagelse (S.A.I.) - all in Denmark; the Department of Intensive Care and Department of Clinical Research, University of Basel, Basel (M.S., A.H., C.E.G., N.Z.), and the Department of Intensive Care, Inselspital, University of Bern, Bern (J.C.S.) - both in Switzerland; the Department of Perioperative, Intensive Care and Pain Medicine, Helsinki University Hospital, Helsinki (M.B., M.O.); the Department of Critical Care, University Medical Center Groningen, Groningen, the Netherlands (F.K., W.D.); the Departments of Anesthesia and Intensive Care and of Clinical Research, Rikshospitalet, Oslo University Hospital, Oslo (J.H.L., T.N.A.); the Department of Intensive Care, Cardiff University Hospital of Wales, Cardiff, United Kingdom (M.M.); and the Department of Anesthesia and Intensive Care, Landspitali University Hospital, Reykjavik, Iceland (K.M.T.).

PMID: 33471452
DOI: 10.1056/NEJMoa2032510

Abstract

Background: Patients with acute hypoxemic respiratory failure in the intensive care unit (ICU) are treated with supplemental oxygen, but the benefits and harms of different oxygenation targets are unclear. We hypothesized that using a lower target for partial pressure of arterial oxygen (Pao₂) would result in lower mortality than using a higher target.

Methods: In this multicenter trial, we randomly assigned 2928 adult patients who had recently been admitted to the ICU (≤12 hours before randomization) and who were receiving at least 10 liters of oxygen per minute in an open system or had a fraction of inspired oxygen of at least 0.50 in a closed system to receive oxygen therapy targeting a Pao₂ of either 60 mm Hg (lower-oxygenation group) or 90 mm Hg (higher-oxygenation group) for a maximum of 90 days. The primary outcome was death within 90 days.

Results: At 90 days, 618 of 1441 patients (42.9%) in the lower-oxygenation group and 613 of 1447 patients (42.4%) in the higher-oxygenation group had died (adjusted risk ratio, 1.02; 95% confidence interval, 0.94 to 1.11; P = 0.64). At 90 days, there was no significant between-group difference in the percentage of days that patients were alive without life support or in the percentage of days they were alive after hospital discharge. The percentages of patients who had new episodes of shock, myocardial ischemia, ischemic stroke, or intestinal ischemia were similar in the two groups (P = 0.24).

Conclusions: Among adult patients with acute hypoxemic respiratory failure in the ICU, a lower oxygenation target did not result in lower mortality than a higher target at 90 days. (Funded by the Innovation Fund Denmark and others; HOT-ICU ClinicalTrials.gov number, NCT03174002.).

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Comment in

Effect of Oxygen Therapy on Mortality in the ICU.
Young PJ. Young PJ. N Engl J Med. 2021 Apr 8;384(14):1361-1363. doi: 10.1056/NEJMe2101538. N Engl J Med. 2021. PMID: 33826824 No abstract available.
[Focus ventilation, oxygen therapy and weaning : Intensive medical care studies from 2020/2021].
Fiedler MO, Reuß CJ, Bernhard M, Beynon C, Hecker A, Jungk C, Nusshag C, Michalski D, Brenner T, Weigand MA, Dietrich M. Fiedler MO, et al. Anaesthesist. 2021 Nov;70(11):967-976. doi: 10.1007/s00101-021-00979-8. Epub 2021 Oct 6. Anaesthesist. 2021. PMID: 34613457 Free PMC article. German. No abstract available.
Similar Clinical Outcomes with Higher and Lower Oxygenation Targets.
Rosenberg K. Rosenberg K. Am J Nurs. 2021 Aug 1;121(8):56. doi: 10.1097/01.NAJ.0000767832.80703.80. Am J Nurs. 2021. PMID: 34819479
Conservative versus Liberal Oxygen Therapy.
Watson N, Brown E, Ritchie AI, Soni S. Watson N, et al. Am J Respir Crit Care Med. 2022 Jun 15;205(12):1470. doi: 10.1164/rccm.202107-1609RR. Am J Respir Crit Care Med. 2022. PMID: 35499956 No abstract available.

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Thille AW, Balen F, Carteaux G, Chouihed T, Frat JP, Girault C, L'Her E, Marjanovic N, Nay MA, Ray P, Reffienna M, Retenauer L, Roch A, Thiery G, Truchot J. Thille AW, et al. Ann Intensive Care. 2024 Oct 18;14(1):158. doi: 10.1186/s13613-024-01389-w. Ann Intensive Care. 2024. PMID: 39419924 Free PMC article. Review.
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Singla D, Tk P, Adhikary AB, Jonna D, Mangla M. Singla D, et al. Cureus. 2024 Aug 26;16(8):e67809. doi: 10.7759/cureus.67809. eCollection 2024 Aug. Cureus. 2024. PMID: 39323662 Free PMC article.
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Oxygen therapy in acute hypoxemic respiratory failure: guidelines from the SRLF-SFMU consensus conference.
Helms J, Catoire P, Abensur Vuillaume L, Bannelier H, Douillet D, Dupuis C, Federici L, Jezequel M, Jozwiak M, Kuteifan K, Labro G, Latournerie G, Michelet F, Monnet X, Persichini R, Polge F, Savary D, Vromant A, Adda I, Hraiech S. Helms J, et al. Ann Intensive Care. 2024 Sep 5;14(1):140. doi: 10.1186/s13613-024-01367-2. Ann Intensive Care. 2024. PMID: 39235690 Free PMC article.

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Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure

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Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure

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