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 Lass

AU - Schjørring, Olav L

AU - Lange, Theis

AU - Møller, Morten H

AU - Perner, Anders

AU - Rasmussen, Bodil Steen

AU - Granholm, Anders

N1 - Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

PY - 2022/1

Y1 - 2022/1

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.

UR - http://www.scopus.com/inward/record.url?scp=85117386463&partnerID=8YFLogxK

U2 - 10.1016/j.bja.2021.09.010

DO - 10.1016/j.bja.2021.09.010

M3 - Journal article

C2 - 34674834

VL - 128

SP - 55

EP - 64

JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

SN - 0007-0912

IS - 1

ER -