Oxygenation targets in ICU patients with COVID-19: a post-hoc sub-group analysis of the HOT-ICU trial

Bodil S Rasmussen; Thomas L Klitgaard; Anders Perner; Björn A Brand; Thomas Hildebrandt; Martin Siegemund; Alexa Hollinger; Søren R Aagaard; Morten H Bestle; Klaus V Marcussen; Anne C Brøchner; Christoffer G Sølling; Lone M Poulsen; Jon H Laake; Tayyba N Aslam; Minna Bäcklund; Marjatta Okkonen; Matthew Morgan; Mike Sharman; Theis Lange; Jørn Wetterslev; Olav L Schjørring

doi:10.1111/aas.13977

Oxygenation targets in ICU patients with COVID-19: a post-hoc sub-group analysis of the HOT-ICU trial

Bodil S Rasmussen^*, Thomas L Klitgaard, Anders Perner, Björn A Brand, Thomas Hildebrandt, Martin Siegemund, Alexa Hollinger, Søren R Aagaard, Morten H Bestle, Klaus V Marcussen, Anne C Brøchner, Christoffer G Sølling, Lone M Poulsen, Jon H Laake, Tayyba N Aslam, Minna Bäcklund, Marjatta Okkonen, Matthew Morgan, Mike Sharman, Theis LangeJørn Wetterslev, Olav L Schjørring

^*Corresponding author for this work

21 Citations (Scopus)

Abstract

BACKGROUND: Supplemental oxygen is the key intervention for severe and critical COVID-19 patients. With the unstable supplies of oxygen in many countries, it is important to define the lowest safe dosage.

METHODS: In spring 2020, 110 COVID-19 patients were enrolled as part of the Handling Oxygenation Targets in the ICU trial (HOT-ICU). Patients were allocated within 12 h of ICU admission. Oxygen therapy was titrated to a partial pressure of arterial oxygen (PaO2 ) of 8 kPa (lower oxygenation group) or a PaO2 of 12 kPa (higher oxygenation group) during ICU stay up to 90 days. We report key outcomes at 90 days for the subgroup of COVID-19 patients.

RESULTS: At 90 days, 22 of 54 patients (40.7%) in the lower oxygenation group and 23 of 55 patients (41.8%) in the higher oxygenation group had died (adjusted risk ratio: 0.87; 95% confidence interval, 0.58-1.32). The percentage of days alive without life support was significantly higher in the lower oxygenation group (p = 0.03). The numbers of severe ischemic events were low with no difference between the two groups. Proning and inhaled vasodilators were used more frequently, and the positive end-expiratory pressure was higher in the higher oxygenation group. Tests for interactions with the results of the remaining HOT-ICU population were insignificant.

CONCLUSIONS: Targeting a PaO2 of 8 kPa may be beneficial in ICU patients with COVID-19. These results come with uncertainty due to the low number of patients in this unplanned subgroup analysis, and insignificant tests for interaction with the main HOT-ICU trial.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT03174002. Date of registration: June 2, 2017.

Original language	English
Journal	Acta Anaesthesiologica Scandinavica
Volume	66
Issue number	1
Pages (from-to)	76-84
Number of pages	9
ISSN	0001-5172
DOIs	https://doi.org/10.1111/aas.13977
Publication status	Published - Jan 2022

Keywords

intensive care units
oxygen inhalation therapy
randomized controlled trial
respiratory insufficiency
severe acute respiratory syndrome coronavirus 2

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10.1111/aas.13977

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Rasmussen, B. S., Klitgaard, T. L., Perner, A., Brand, B. A., Hildebrandt, T., Siegemund, M., Hollinger, A., Aagaard, S. R., Bestle, M. H., Marcussen, K. V., Brøchner, A. C., Sølling, C. G., Poulsen, L. M., Laake, J. H., Aslam, T. N., Bäcklund, M., Okkonen, M., Morgan, M., Sharman, M., ... Schjørring, O. L. (2022). Oxygenation targets in ICU patients with COVID-19: a post-hoc sub-group analysis of the HOT-ICU trial. Acta Anaesthesiologica Scandinavica, 66(1), 76-84. https://doi.org/10.1111/aas.13977

Rasmussen, BS, Klitgaard, TL, Perner, A, Brand, BA, Hildebrandt, T, Siegemund, M, Hollinger, A, Aagaard, SR, Bestle, MH, Marcussen, KV, Brøchner, AC, Sølling, CG, Poulsen, LM, Laake, JH, Aslam, TN, Bäcklund, M, Okkonen, M, Morgan, M, Sharman, M, Lange, T, Wetterslev, J & Schjørring, OL 2022, 'Oxygenation targets in ICU patients with COVID-19: a post-hoc sub-group analysis of the HOT-ICU trial', Acta Anaesthesiologica Scandinavica, vol. 66, no. 1, pp. 76-84. https://doi.org/10.1111/aas.13977

@article{26b51b40d88948978de6f7c9c653cf0b,

title = "Oxygenation targets in ICU patients with COVID-19: a post-hoc sub-group analysis of the HOT-ICU trial",

abstract = "BACKGROUND: Supplemental oxygen is the key intervention for severe and critical COVID-19 patients. With the unstable supplies of oxygen in many countries, it is important to define the lowest safe dosage.METHODS: In spring 2020, 110 COVID-19 patients were enrolled as part of the Handling Oxygenation Targets in the ICU trial (HOT-ICU). Patients were allocated within 12 h of ICU admission. Oxygen therapy was titrated to a partial pressure of arterial oxygen (PaO2 ) of 8 kPa (lower oxygenation group) or a PaO2 of 12 kPa (higher oxygenation group) during ICU stay up to 90 days. We report key outcomes at 90 days for the subgroup of COVID-19 patients.RESULTS: At 90 days, 22 of 54 patients (40.7\%) in the lower oxygenation group and 23 of 55 patients (41.8\%) in the higher oxygenation group had died (adjusted risk ratio: 0.87; 95\% confidence interval, 0.58-1.32). The percentage of days alive without life support was significantly higher in the lower oxygenation group (p = 0.03). The numbers of severe ischemic events were low with no difference between the two groups. Proning and inhaled vasodilators were used more frequently, and the positive end-expiratory pressure was higher in the higher oxygenation group. Tests for interactions with the results of the remaining HOT-ICU population were insignificant.CONCLUSIONS: Targeting a PaO2 of 8 kPa may be beneficial in ICU patients with COVID-19. These results come with uncertainty due to the low number of patients in this unplanned subgroup analysis, and insignificant tests for interaction with the main HOT-ICU trial.TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT03174002. Date of registration: June 2, 2017.",

keywords = "intensive care units, oxygen inhalation therapy, randomized controlled trial, respiratory insufficiency, severe acute respiratory syndrome coronavirus 2",

author = "Rasmussen, \{Bodil S\} and Klitgaard, \{Thomas L\} and Anders Perner and Brand, \{Bj{\"o}rn A\} and Thomas Hildebrandt and Martin Siegemund and Alexa Hollinger and Aagaard, \{S{\o}ren R\} and Bestle, \{Morten H\} and Marcussen, \{Klaus V\} and Br{\o}chner, \{Anne C\} and S{\o}lling, \{Christoffer G\} and Poulsen, \{Lone M\} and Laake, \{Jon H\} and Aslam, \{Tayyba N\} and Minna B{\"a}cklund and Marjatta Okkonen and Matthew Morgan and Mike Sharman and Theis Lange and J{\o}rn Wetterslev and Schj{\o}rring, \{Olav L\}",

year = "2022",

month = jan,

doi = "10.1111/aas.13977",

language = "English",

volume = "66",

pages = "76--84",

journal = "Acta Anaesthesiologica Scandinavica",

issn = "0001-5172",

publisher = "Blackwell Munksgaard",

number = "1",

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TY - JOUR

T1 - Oxygenation targets in ICU patients with COVID-19

T2 - a post-hoc sub-group analysis of the HOT-ICU trial

AU - Rasmussen, Bodil S

AU - Klitgaard, Thomas L

AU - Perner, Anders

AU - Brand, Björn A

AU - Hildebrandt, Thomas

AU - Siegemund, Martin

AU - Hollinger, Alexa

AU - Aagaard, Søren R

AU - Bestle, Morten H

AU - Marcussen, Klaus V

AU - Brøchner, Anne C

AU - Sølling, Christoffer G

AU - Poulsen, Lone M

AU - Laake, Jon H

AU - Aslam, Tayyba N

AU - Bäcklund, Minna

AU - Okkonen, Marjatta

AU - Morgan, Matthew

AU - Sharman, Mike

AU - Lange, Theis

AU - Wetterslev, Jørn

AU - Schjørring, Olav L

PY - 2022/1

Y1 - 2022/1

N2 - BACKGROUND: Supplemental oxygen is the key intervention for severe and critical COVID-19 patients. With the unstable supplies of oxygen in many countries, it is important to define the lowest safe dosage.METHODS: In spring 2020, 110 COVID-19 patients were enrolled as part of the Handling Oxygenation Targets in the ICU trial (HOT-ICU). Patients were allocated within 12 h of ICU admission. Oxygen therapy was titrated to a partial pressure of arterial oxygen (PaO2 ) of 8 kPa (lower oxygenation group) or a PaO2 of 12 kPa (higher oxygenation group) during ICU stay up to 90 days. We report key outcomes at 90 days for the subgroup of COVID-19 patients.RESULTS: At 90 days, 22 of 54 patients (40.7%) in the lower oxygenation group and 23 of 55 patients (41.8%) in the higher oxygenation group had died (adjusted risk ratio: 0.87; 95% confidence interval, 0.58-1.32). The percentage of days alive without life support was significantly higher in the lower oxygenation group (p = 0.03). The numbers of severe ischemic events were low with no difference between the two groups. Proning and inhaled vasodilators were used more frequently, and the positive end-expiratory pressure was higher in the higher oxygenation group. Tests for interactions with the results of the remaining HOT-ICU population were insignificant.CONCLUSIONS: Targeting a PaO2 of 8 kPa may be beneficial in ICU patients with COVID-19. These results come with uncertainty due to the low number of patients in this unplanned subgroup analysis, and insignificant tests for interaction with the main HOT-ICU trial.TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT03174002. Date of registration: June 2, 2017.

AB - BACKGROUND: Supplemental oxygen is the key intervention for severe and critical COVID-19 patients. With the unstable supplies of oxygen in many countries, it is important to define the lowest safe dosage.METHODS: In spring 2020, 110 COVID-19 patients were enrolled as part of the Handling Oxygenation Targets in the ICU trial (HOT-ICU). Patients were allocated within 12 h of ICU admission. Oxygen therapy was titrated to a partial pressure of arterial oxygen (PaO2 ) of 8 kPa (lower oxygenation group) or a PaO2 of 12 kPa (higher oxygenation group) during ICU stay up to 90 days. We report key outcomes at 90 days for the subgroup of COVID-19 patients.RESULTS: At 90 days, 22 of 54 patients (40.7%) in the lower oxygenation group and 23 of 55 patients (41.8%) in the higher oxygenation group had died (adjusted risk ratio: 0.87; 95% confidence interval, 0.58-1.32). The percentage of days alive without life support was significantly higher in the lower oxygenation group (p = 0.03). The numbers of severe ischemic events were low with no difference between the two groups. Proning and inhaled vasodilators were used more frequently, and the positive end-expiratory pressure was higher in the higher oxygenation group. Tests for interactions with the results of the remaining HOT-ICU population were insignificant.CONCLUSIONS: Targeting a PaO2 of 8 kPa may be beneficial in ICU patients with COVID-19. These results come with uncertainty due to the low number of patients in this unplanned subgroup analysis, and insignificant tests for interaction with the main HOT-ICU trial.TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT03174002. Date of registration: June 2, 2017.

KW - intensive care units

KW - oxygen inhalation therapy

KW - randomized controlled trial

KW - respiratory insufficiency

KW - severe acute respiratory syndrome coronavirus 2

UR - https://www.scopus.com/pages/publications/85115101315

U2 - 10.1111/aas.13977

DO - 10.1111/aas.13977

M3 - Journal article

C2 - 34425016

SN - 0001-5172

VL - 66

SP - 76

EP - 84

JO - Acta Anaesthesiologica Scandinavica

JF - Acta Anaesthesiologica Scandinavica

IS - 1

ER -

Oxygenation targets in ICU patients with COVID-19: a post-hoc sub-group analysis of the HOT-ICU trial

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