Long-term effects of lower versus higher oxygenation levels in adult ICU patients—A systematic review

BACKGROUND: Oxygen therapy is a common treatment in the intensive care unit (ICU) with both potentially desirable and undesirable long‐term effects. This systematic review aimed to assess the long‐term outcomes of lower versus higher oxygenation strategies in adult ICU survivors. METHODS: We included randomised clinical trials (RCTs) comparing lower versus higher oxygen supplementation or oxygenation strategies in adults admitted to the ICU. We searched major electronic databases and trial registers. We included all non‐mortality long‐term outcomes. Prespecified co‐primary outcomes were the long‐term cognitive function measures, the overall score of any valid health‐related quality of life (HRQoL) evaluation, standardised 6‐min walk test, and lung diffusion capacity. The protocol was published and prospectively registered in the PROSPERO database (CRD42021223630). RESULTS: The review included 17 RCTs comprising 6592 patients, and six trials with 825 randomised patients reported one or more outcomes of interest. We observed no difference in cognitive evaluation via Telephone Interview for Cognitive Status (one trial, 409 patients) (mean score: 30.6 ± 4.5 in the lower oxygenation group vs. 30.4 ± 4.3 in the higher oxygenation group). The trial was judged at overall high risk of bias and the certainty of evidence was very low. Any difference was neither observed in HRQoL measured via EuroQol 5 dimensions 5 level questionnaire and EQ Visual Analogue Score (one trial, 499 patients) (mean score: 70.1 ± 22 in the lower oxygenation group vs. 67.6 ± 22.4 in the higher oxygenation group). The trial was judged as having high risk of bias, the certainty of evidence was very low. No trial reported neither the standardised 6‐min walk test nor lung diffusion test. CONCLUSION: The evidence is very uncertain about the effect of a lower versus a higher oxygenation strategy on both the cognitive function and HRQoL. A lower versus a higher oxygenation strategy may have a little to no effect on both outcomes but the certainty of evidence is very low. No evidence was found for the effects on the standardised 6‐min walking test and diffusion capacity test

Causal inference for planning randomised critical care trials:Protocol for a scoping review

BACKGROUND: Randomised clinical trials in critical care are prone to inconclusiveness owing, in part, to undue optimism about effect sizes and suboptimal accounting for heterogeneous treatment effects. Planned predictive enrichment based on secondary critical care data (often very rich with respect to both data types and temporal granularity) and causal inference methods may help overcome these challenges, but no overview exists about their use to this end. METHODS: We will conduct a scoping review to assess the extent and nature of the use of causal inference from secondary data for planned predictive enrichment of randomised clinical trials in critical care. We will systematically search 10 general and specialty journals for reports published on or after 1 January 2018, of randomised clinical trials enrolling adult critically ill patients. We will collect trial metadata (e.g., recruitment period and phase) and, when available, information pertaining to the focus of the review (predictive enrichment based on causal inference estimates from secondary data): causal inference methods, estimation techniques and software used; types of patient populations; data provenance, types and models; and the availability of the data (public or not). The results will be reported in a descriptive manner. DISCUSSION: The outlined scoping review aims to assess the use of causal inference methods and secondary data for planned predictive enrichment in randomised critical care trials. This will help guide methodological improvements to increase the utility, and facilitate the use, of causal inference estimates when planning such trials in the future