Rationale: Supplemental oxygen is widely administered to ICU patients, but appropriate oxygenation targets remain unclear. Objectives: This study aimed to determine whether a low-oxygenation strategy would lower 28-day mortality compared with a high-oxygenation strategy. Methods: This randomized multicenter trial included mechanically ventilated ICU patients with an expected ventilation duration of at least 24 hours. Patients were randomized 1:1 to a low-oxygenation (PaO2, 55–80 mm Hg; or oxygen saturation as measured by pulse oximetry, 91–94%) or high-oxygenation (PaO2, 110–150 mm Hg; or oxygen saturation as measured by pulse oximetry, 96–100%) target until ICU discharge or 28 days after randomization, whichever came first. The primary outcome was 28-day mortality. The study was stopped prematurely because of the COVID-19 pandemic when 664 of the planned 1,512 patients were included. Measurements and Main Results: Between November 2018 and November 2021, a total of 664 patients were included in the trial: 335 in the low-oxygenation group and 329 in the high-oxygenation group. The median achieved PaO2 was 75 mm Hg (interquartile range, 70–84) and 115 mm Hg (interquartile range, 100–129) in the low- and high-oxygenation groups, respectively. At Day 28, 129 (38.5%) and 114 (34.7%) patients had died in the low- and high-oxygenation groups, respectively (risk ratio, 1.11; 95% confidence interval, 0.9–1.4; P = 0.30). At least one serious adverse event was reported in 12 (3.6%) and 17 (5.2%) patients in the low- and high-oxygenation groups, respectively. Conclusions: Among mechanically ventilated ICU patients with an expected mechanical ventilation duration of at least 24 hours, using a low-oxygenation strategy did not result in a reduction of 28-day mortality compared with a high-oxygenation strategy. Clinical trial registered with the National Trial Register and the International Clinical Trials Registry Platform (NTR7376).

Oxygen therapy is vital in adult intensive care unit (ICU) patients, but it is indistinct whether higher or lower oxygen targets are favorable. Our aim was to update the findings of randomized controlled trials (RTCs) comparing higher and lower oxygen strategies. MEDLINE, EMBASE, and Web of Science were searched. RCTs comparing higher (liberal, hyperoxia) and lower (conservative, normoxia) oxygen in adult mechanically ventilated ICU patients were included. The main outcome was 90-day mortality; other outcomes include serious adverse events (SAE), support free days and length of stay (LOS). No significant difference was observed for 90-day mortality. A lower incidence was found for SAEs, favoring lower oxygenation (OR, 0.86; 95%CI, 0.77-0.96; I ² 13%). No differences were observed in either support free days at day 28 or ICU and hospital LOS. No difference was found for 90-day mortality, support free days and ICU and hospital LOS. However, a lower incidence of SAEs was found for lower oxygenation. These findings may have clinical implications for practice guidelines, yet it remains of paramount importance to continue conducting clinical trials, comparing groups with a clinically relevant contrast and focusing on the impact of important side effects.

OBJECTIVES: Deferred consent enables research to be conducted in the ICU when patients are unable to provide consent themselves, and there is insufficient time to obtain consent from surrogates before commencing (trial) treatment. The aim of this study was to evaluate how former ICU patients reflect on their participation in a study with deferred consent and examine whether their opinions are influenced by the quality of life (QoL) following hospital discharge. DESIGN: Survey study by questionnaire. SETTING: Eight ICUs in The Netherlands. PATIENTS: Former ICU patients who participated in the ICONIC trial, a multicenter randomized clinical trial that evaluated oxygenation targets in mechanically ventilated ICU patients. INTERVENTIONS: Participants enrolled in the ICONIC trial in one of the eight participating centers in The Netherlands received a questionnaire 6 months after randomization. The questionnaire included 12 close-ended questions on their opinion about the deferred consent procedure. QoL was measured using the EQ-5D-5L questionnaire. By calculating the EQ-5D index, patients were divided into four QoL quartiles, where Q1 reflects the lowest and Q4 is the highest. MEASUREMENTS AND MAIN RESULTS: Of 362 participants who were contacted, 197 responded (54%). More than half of the respondents (59%) were unaware of their participation in the ICONIC study. In total 61% were content with the deferred consent procedure, 1% were not content, 25% neutral, 9% did not know, and 9% answered “other.” Those with a higher QoL were more likely to be content (p = 0.02). In all QoL groups, the legal representative was the most often preferred individual to provide consent. CONCLUSIONS: Former ICU patients who participated in the ICONIC study often did not remember their participation but were predominantly positive regarding the use of deferred consent. Those with a higher QoL were most likely to be content.

Background: Oxygen therapy is a widely used intervention in acutely ill patients in the intensive care unit (ICU). It is established that not only hypoxia, but also prolonged hyperoxia is associated with poor patient-centered outcomes. Nevertheless, a fundamental knowledge gap remains regarding optimal oxygenation for critically ill patients. In this randomized clinical trial, we aim to compare ventilation that uses conservative oxygenation targets with ventilation that uses conventional oxygen targets with respect to mortality in ICU patients.Methods: The “ConservatIve versusCONventional oxygenation targets inIntensiveCare patients” trial (ICONIC) is an investigator-initiated, international, multicenter, randomized clinical two-arm trial in ventilated adult ICU patients. The ICONIC trial will run in multiple ICUs in The Netherlands and Italy to enroll 1512 ventilated patients. ICU patients with an expected mechanical ventilation time of more than 24 h are randomized to a ventilation strategy that uses conservative (PaO₂55–80 mmHg (7.3–10.7 kPa)) or conventional (PaO₂110–150 mmHg (14.7–20 kPa)) oxygenation targets. The primary endpoint is 28-day mortality. Secondary endpoints are ventilator-free days at day 28, ICU mortality, in-hospital mortality, 90-day mortality, ICU- and hospital length of stay, ischemic events, quality of life, and patient opinion of research and consent in the emergency setting.Discussion: The ICONIC trial is expected to provide evidence on the effects of conservative versus conventional oxygenation targets in the ICU population. This study may guide targeted oxygen therapy in the future.Trial registration: Trialregister.nlNTR7376. Registered on 20 July, 2018.

BackgroundOxygen therapy is vital in intensive care unit (ICU) patients, but it is indistinct whether higher or lower oxygen targets are favorable with regards to patient centered outcomes. Our aim was to systematically evaluate the findings of randomized controlled trials (RTCs) comparing higher and lower oxygen therapy strategies in mechanically ventilated patients.MethodsA meta-analysis and meta-regression analysis of RCTs published between 2015 and 2021 was conducted. Electronic databases of MEDLINE, EMBASE, and Web of Science were systematically searched. Publications comparing the effects of higher or lower oxygen therapy in adult ICU patients were eligible. Risk of bias was assessed using the Cochrane Risk of Bias tool. The primary outcome was mortality at day 90; secondary outcomes include serious adverse events (SAE), ICU and hospital length of stay and support-free days.ResultsWe included nine RCTs enrolling 5807 patients. No significant difference was observed for mortality at day 90. A significantly lower odds ratio (OR) was found for SAEs, favoring lower oxygenation (OR 0.86 [0.77, 0.96], P=0.009). Our meta-regression analysis shows that the effect sizes for 90-day mortality may be influenced by both the between-group difference in achieved oxygenation and the severity of hyperoxia in the higher group (ß=-0.0022, P=0.1).ConclusionIn the general ICU population, there was no significant difference in 90-day mortality between higher and lower oxygenation strategies. However, a lower incidence of serious adverse events was found for the lower oxygenation groups. These findings may have clinical implications for practice guidelines, yet it remains of paramount importance to continue conducting clinical trials, ideally comparing groups with a clinically relevant contrast for specific patient groups.Trial registrationThe protocol of this study was registered on PROSPERO (CRD42021286372).