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.

中文翻译：

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严重低氧血症危重患者的较低氧合目标与较高氧合目标：二次贝叶斯分析探讨重症监护病房 (HOT-ICU) 试验中处理氧合目标的异质性治疗效果

 背景

在重症监护病房 (HOT-ICU) 处理氧合目标试验中，较低 (8 kPa)与较高 (12 kPa) PaO ₂目标不会影响危重成年患者的死亡率。我们使用贝叶斯统计来评估 HOT-ICU 试验中不同患者组之间氧合目标对死亡率影响的异质性。

 方法

我们使用调整后的贝叶斯逻辑回归模型分析了 90 天全因死亡率，并使用亚组分层模型和连续尺度上的交互模型根据四个选定的基线变量评估异质治疗效果。结果以死亡率概率 (%) 和相对风险 (RR) 表示，可信区间 (CrI) 为 95%。

 结果

HOT-ICU 试验意向治疗队列中的所有 2888 名患者均被纳入。低氧组和高氧组的调整后 90 天死亡率分别为 43.0% (CrI: 38.3–47.8%) 和 42.3% (CrI: 37.7–47.1%) (RR 1.02 [CrI: 0.93–1.11])， RR <1.00 的概率为 36.5%。对异质性治疗效果的分析表明，基线去甲肾上腺素剂量与较低氧合目标死亡率增加之间存在剂量反应关系，随着去甲肾上腺素剂量增加，死亡率增加的可能性为 95%。

 结论

较低的氧合目标不太可能影响患有急性低氧性呼吸衰竭的危重成年患者的总体死亡率。然而，我们的结果表明，随着基线去甲肾上腺素剂量的增加，氧目标较低的患者的死亡风险会增加。这些发现值得进一步调查。

临床试验注册

 NCT03174002。