Lower versus higher oxygenation targets in critically ill patients with severe hypoxaemia: secondary Bayesian analysis to explore heterogeneous treatment effects in the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial
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Lower versus higher oxygenation targets in critically ill patients with severe hypoxaemia : secondary Bayesian analysis to explore heterogeneous treatment effects in the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial. / Klitgaard, Thomas L.; Schjørring, Olav L.; Lange, Theis; Møller, Morten H.; Perner, Anders; Rasmussen, Bodil S.; Granholm, Anders.
In: British Journal of Anaesthesia, Vol. 128, No. 1, 2022, p. 55-64.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Lower versus higher oxygenation targets in critically ill patients with severe hypoxaemia
T2 - secondary Bayesian analysis to explore heterogeneous treatment effects in the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial
AU - Klitgaard, Thomas L.
AU - Schjørring, Olav L.
AU - Lange, Theis
AU - Møller, Morten H.
AU - Perner, Anders
AU - Rasmussen, Bodil S.
AU - Granholm, Anders
N1 - Publisher Copyright: © 2021 The Author(s)
PY - 2022
Y1 - 2022
N2 - Background: In the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial, a lower (8 kPa) vs a higher (12 kPa) PaO2 target did not affect mortality amongst critically ill adult patients. We used Bayesian statistics to evaluate any heterogeneity in the effect of oxygenation targets on mortality between different patient groups within the HOT-ICU trial. Methods: We analysed 90-day all-cause mortality using adjusted Bayesian logistic regression models, and assessed heterogeneous treatment effects according to four selected baseline variables using both hierarchical models of subgroups and models with interactions on the continuous scales. Results are presented as mortality probability (%) and relative risk (RR) with 95% credibility intervals (CrI). Results: All 2888 patients in the intention-to-treat cohort of the HOT-ICU trial were included. The adjusted 90-day mortality rates were 43.0% (CrI: 38.3–47.8%) and 42.3% (CrI: 37.7–47.1%) in the lower and higher oxygenation groups, respectively (RR 1.02 [CrI: 0.93–1.11]), with 36.5% probability of an RR <1.00. Analyses of heterogeneous treatment effects suggested a dose–response relationship between baseline norepinephrine dose and increased mortality with the lower oxygenation target, with 95% probability of increased mortality associated with the lower oxygenation target as norepinephrine doses increased. Conclusions: A lower oxygenation target was unlikely to affect overall mortality amongst critically ill adult patients with acute hypoxaemic respiratory failure. However, our results suggest an increasing mortality risk for patients with a lower oxygen target as the baseline norepinephrine dose increases. These findings warrant additional investigation. Clinical trial registration: NCT03174002.
AB - Background: In the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial, a lower (8 kPa) vs a higher (12 kPa) PaO2 target did not affect mortality amongst critically ill adult patients. We used Bayesian statistics to evaluate any heterogeneity in the effect of oxygenation targets on mortality between different patient groups within the HOT-ICU trial. Methods: We analysed 90-day all-cause mortality using adjusted Bayesian logistic regression models, and assessed heterogeneous treatment effects according to four selected baseline variables using both hierarchical models of subgroups and models with interactions on the continuous scales. Results are presented as mortality probability (%) and relative risk (RR) with 95% credibility intervals (CrI). Results: All 2888 patients in the intention-to-treat cohort of the HOT-ICU trial were included. The adjusted 90-day mortality rates were 43.0% (CrI: 38.3–47.8%) and 42.3% (CrI: 37.7–47.1%) in the lower and higher oxygenation groups, respectively (RR 1.02 [CrI: 0.93–1.11]), with 36.5% probability of an RR <1.00. Analyses of heterogeneous treatment effects suggested a dose–response relationship between baseline norepinephrine dose and increased mortality with the lower oxygenation target, with 95% probability of increased mortality associated with the lower oxygenation target as norepinephrine doses increased. Conclusions: A lower oxygenation target was unlikely to affect overall mortality amongst critically ill adult patients with acute hypoxaemic respiratory failure. However, our results suggest an increasing mortality risk for patients with a lower oxygen target as the baseline norepinephrine dose increases. These findings warrant additional investigation. Clinical trial registration: NCT03174002.
KW - Bayesian analysis
KW - heterogeneity of treatment effects
KW - intensive care unit
KW - oxygen therapy
KW - respiratory insufficiency
U2 - 10.1016/j.bja.2021.09.010
DO - 10.1016/j.bja.2021.09.010
M3 - Journal article
C2 - 34674834
AN - SCOPUS:85117386463
VL - 128
SP - 55
EP - 64
JO - British Journal of Anaesthesia
JF - British Journal of Anaesthesia
SN - 0007-0912
IS - 1
ER -
ID: 286996148