Association between days alive without life support/out of hospital and health-related quality of life.

BACKGROUND: Trials in critically ill patients increasingly focus on days alive without life support (DAWOLS) or days alive out of hospital (DAOOH) and health-related quality of life (HRQoL). DAWOLS and DAOOH convey more information than mortality and are simpler and faster to collect than HRQoL. However, whether these outcomes are associated with HRQoL is uncertain. We thus aimed to assess the associations between DAWOLS and DAOOH and long-term HRQoL. METHODS: Secondary analysis of the COVID STEROID 2 trial including adults with COVID-19 and severe hypoxaemia and the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial including adult intensive care unit patients with acute hypoxaemic respiratory failure. Associations between DAWOLS and DAOOH at day 28 and 90 and long-term HRQoL (after 6 or 12 months) using the EuroQol 5-dimension 5-level survey (EQ VAS and EQ-5D-5L index values) were assessed using flexible models and evaluated using measures of fit and prediction adequacy in both datasets (comprising internal performance and external validation), non-parametric correlation coefficients and graphical presentations. RESULTS: We found no strong associations between DAWOLS or DAOOH and HRQoL in survivors at HRQoL-follow-up (615 and 1476 patients, respectively). There was substantial variability in outcomes, and predictions from the best fitted models were poor both internally and externally in the other trial dataset, which also showed inadequate calibration. Moderate associations were found when including non-survivors, although predictions remained uncertain and calibration inadequate. CONCLUSION: DAWOLS and DAOOH were poorly associated with HRQoL in adult survivors of severe or critical illness included in the COVID STEROID 2 and HOT-ICU trials.

Health-related quality of life and days alive without life support or out of hospital: Protocol.

BACKGROUND: Mortality is often the primary outcome in randomised clinical trials (RCTs) conducted in critically ill patients. Due to increased awareness on survivors after critical illness and outcomes other than mortality, health-related quality of life (HRQoL) and days alive without life support (DAWOLS) or days alive and out of hospital (DAAOOH) are increasingly being used. DAWOLS and DAAOOH convey more information than mortality, are easier to collect than HRQoL, and are usually assessed at earlier time points, which may be preferable in some situations. However, the associations between DAWOLS-DAAOOH and HRQoL are uncertain. METHODS: We will assess associations between DAWOLS-DAAOOH at day 28 and 90 (independent variables/predictors) and HRQoL assessed using the EuroQol EQ-5D-5L questionnaire (EQ-VAS and EQ-5D-5L index values) at 6 or 12 months (dependent variables) in two RCTs: the COVID STEROID 2 RCT conducted in adult patients with COVID-19 and severe hypoxaemia and the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) RCT conducted in adult intensive care patients with acute hypoxaemic respiratory failure. We will describe associations using best-fitting fractional polynomial transformations separately in each dataset, with the resulting models presented and assessed in both datasets graphically and using measures of fit and prediction adequacy (i.e., internal performance and external validation). We will use multiple imputation if missingness exceeds 5%. DISCUSSION: The outlined study will provide important knowledge on the associations between DAWOLS-DAAOOH and HRQoL in adult critically ill patients, which may help researchers and clinical trialists prioritise and select outcomes in future RCTs conducted in this population.

The long-term effects of lower versus higher oxygenation levels in adult ICU patients - protocol for a systematic review.

BACKGROUND: Many organs can remain impaired after discharge from the intensive care unit (ICU) leading to temporal or permanent dysfunctions. Long-term impairments may be affected by supplemental oxygen, a common treatment in ICU, having both potential beneficial and harmful long-lasting effects. This systematic review aims to assess the long-term outcomes of lower versus higher oxygen supplementation and/or oxygenation levels in adults admitted to ICU. METHODS: We will include trials differentiating between a lower and a higher oxygen supplementation or a lower and a higher oxygenation strategy in adults admitted to the ICU. We will search major electronic databases and trial registers for randomised clinical trials. Two authors will independently screen and select references for inclusion using Covidence and predefined data will be extracted. The methodological quality and risk of bias of included trials will be evaluated using the Cochrane Risk of Bias tool 2. Meta-analysis will be performed if two or more trials with comparable outcome measures will be included. Otherwise, a narrative description of the trials' results will be presented instead. To assess the certainty of evidence, we will create a 'Summary of findings' table containing all prespecified outcomes using the GRADE system. The protocol is submitted on the PROSPERO database (ID 223630). CONCLUSION: No systematic reviews on the impact of oxygen treatment in the ICU on long-term outcomes, other than mortality and quality of life, have been reported yet. This systematic review will provide an overview of the current evidence and will help future research in the field.

Handling oxygenation targets in ICU patients with COVID-19-Protocol and statistical analysis plan in the HOT-COVID trial.

BACKGROUND: Coronavirus disease (COVID-19) primarily affects the lungs and lower airways and may present as hypoxaemic respiratory failure requiring admission to an intensive care unit (ICU) for supportive treatment. Here, supplemental oxygen remains essential for COVID-19 patient management, but the optimal dosage is not defined. We hypothesize that targeting an arterial partial pressure of oxygen of 8 kPa throughout ICU admission is superior to targeting 12 kPa. METHODS: The Handling Oxygenation Targets in ICU patients with COVID-19 (HOT-COVID) trial, is an investigator-initiated, pragmatic, multicentre, randomized, parallel-group trial comparing a lower oxygenation target versus a higher oxygenation target in adult ICU patients with COVID-19. The primary outcome is days alive without life-support (use of mechanical ventilation, renal replacement therapy or vasoactive therapy) at day 90. Secondary outcomes are 90-day and 1-year mortality, serious adverse events in the ICU and days alive and out of hospital in the 90-day period, health-related quality-of-life at 1 year, and health economic analyses. One-year follow-up of cognitive and pulmonary function is planned in a subgroup of Danish patients. We will include 780 patients to detect or reject an absolute increase in days alive without life-support of 7 days with an α of 5% and a ß of 20%. An interim analysis is planned after 90-day follow-up of 390 patients. CONCLUSIONS: The HOT-COVID trial will provide patient-important data on the effect of two oxygenation targets in ICU patients with COVID-19 and hypoxia. This protocol paper describes the background, design and statistical analysis plan for the trial.