Oxygenation targets in ICU patients with COVID-19: A post hoc subgroup 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, 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

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.

Conflict of interest statement

The authors report no conflicts of interest.

© 2021 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Assessment, randomization, and follow‐up of COVID‐19 patients enrolled in the HOT‐ICU trial comparing a lower versus a higher oxygenation target in the ICU
FIGURE 2
FIGURE 2
PaO2, FiO2, and SaO2 by allocation group presented in figures (a), (b) and (c), respectively. The medians of daily means of the partial pressure of arterial oxygen (PaO2), the fraction of inspired oxygen (FiO2), and the arterial oxygen saturation (SaO2) in the ICU up until day 90. Daily means were calculated from the 12‐h lowest and highest PaO2 with concomitant values for FiO2 and SaO2. Bars represent interquartile ranges (IQR). IQR are missing for some points as there is only one measurement for these particular days, see Table S1 in the supplement for patient numbers by days. SaO2 values were not available in blood gas analyses from one site and were therefore missing for 19 patients
FIGURE 3
FIGURE 3
Kaplan–Meier plots of survival. The unadjusted hazard ratio is 0.98 [(95% CI 0.55–1.75, p = 0.98)] and the hazard ratio adjusted for the stratification variables chronic obstructive pulmonary disease, hematological malignancy, and site was 0.82 with 95% CI, 0.45–1.50 (p = 0.94)

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