Conservative versus liberal oxygen therapy in mechanically ventilated patients: A systematic review with meta-analysis

To compare the efficacy and safety of conservative and conventional oxygen therapy in critically ill patients. Relevant literature and randomized controlled trials (RCTs) about the effect of conservative oxygen therapy and conventional oxygen therapy on the prognosis of intensive care unit (ICU) critically ill patients was searched from CNKI, VIP, Wanfang Data, Chinese Clinical Trial Registry, PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov by using the keywords "critically ill patients, conservative oxygen therapy, liberal oxygen therapy, conventional oxygen therapy, mortality" until October 30th in 2018. The main outcome indicators were short-term mortality (28-day mortality or ICU mortality); secondary indicators were 90-day mortality, duration of mechanical ventilation, the length of ICU stay, total hospitalization time, new infection rate in ICU and incidence of new organ dysfunction in ICU. In the conservative oxygen therapy group, the aim of pulse oxygen saturation (SpO2) was 0.90-0.92 or the arterial partial oxygen pressure (PaO2) was 70-100 mmHg (1 mmHg = 0.133 kPa), while in conventional oxygen therapy group SpO2 > 0.96 or PaO2 > 150 mmHg. Literature search, quality evaluation and data extraction was conducted independently by the two authors. The quality of these study was evaluated using Cochrane risk deviation assessment tool, and the relevant data were analyzed using RevMan 5.3 software. Four studies were included in the analysis, these studies were assessed as moderate to high quality studies. A total of 1 076 patients were enrolled, with 539 in the conservative oxygen therapy group and 537 in the conventional oxygen therapy group. Compared with conventional oxygen therapy group, short-term mortality [odds ratio (OR) = 0.66, 95% confidence interval (95%CI) = 0.50-0.87, P = 0.003] and the incidence of new organ dysfunction in ICU (OR = 0.64, 95%CI = 0.41-0.99, P = 0.04) were significantly decreased in conservative oxygen therapy group, duration of mechanical ventilation was significantly prolonged [standardized mean difference (SMD) = 17.17, 95%CI = 7.14-27.21, P = 0.000 8]. But there was no significantly difference in 90-day mortality (OR = 0.83, 95%CI = 0.59-1.17, P = 0.28), new infection rate in ICU (OR = 0.90, 95%CI = 0.66-1.21, P = 0.47), the length of ICU stay (SMD = -0.22, 95%CI = -1.02-0.59, P = 0.60) and total hospitalization time (SMD = 1.44, 95%CI = -1.43-4.31, P = 0.32) between the two groups. Compared with conventional oxygen therapy, conservative oxygen therapy can reduce short-term mortality and the incidence of organ dysfunction in critically ill patients, but cannot decrease the length of ICU stay and total hospitalization time.

Background: The optimal oxygen therapy strategy for critically ill patients remains controversial. This systematic review and meta-analysis evaluated the comparative efficacy of liberal versus conservative oxygen therapy (COT) on mortality and clinical outcomes in a critically ill population. Methods: We conducted a comprehensive search of PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) published from database inception through December 4, 2024. Eligible studies included adult critically ill patients randomized to different oxygen therapy strategies. The primary outcome was short-term mortality (28/30-day), with secondary outcomes encompassing longer-term mortality (90 days and 180 days), healthcare-associated infections, organ dysfunctions, intensive care unit (ICU) and hospital length of stays, and mechanical ventilation parameters. Effect estimates were reported as relative risk (RR) or mean difference with a corresponding 95% confidence interval (CI). Results: Twenty-one RCTs comprising 11,901 patients were studied. COT demonstrated no significant difference in short-term mortality compared to liberal strategies (RR: 0.98; 95% CI: 0.90-1.06; P = 0.27; I2 = 19.8%). Similarly, no differences were observed in 90-day mortality (RR: 0.98; 95% CI: 0.98-1.04; P = 0.72; I2 = 0) or in 180-day mortality (RR: 0.97; 95% CI: 0.84-1.11; P = 0.89; I2 = 0). Both approaches yielded comparable outcomes regarding ICU mortality, ICU and hospital lengths of stay, new-organ dysfunctions, healthcare-associated infections, and mechanical ventilation duration metrics. The trial sequential analysis confirmed sufficient evidence to establish equivalence between the two oxygenation strategies. Conclusion: This comprehensive meta-analysis provides robust evidence that conservative and liberal oxygen therapy approaches yield equivalent mortality and clinical outcomes in critically ill patients. Clinicians should individualize oxygen therapy based on patient-specific factors rather than adopting a standardized approach.

Background: The liberal use of supplemental oxygen therapy is common in intensive care units (ICUs) for critically ill patients, but this practice still lacks high-quality evidence, especially for patients receiving mechanical ventilation (MV). We systematically reviewed the effects of conservative versus liberal oxygen therapy in critically ill adults. Methods: We searched the following electronic databases, including dates from Jan 1st, 2001 until Nov 31st, 2018: PubMed/MEDLINE, Embase, the Cochrane (Central) database and Ovid. Randomized controlled clinical trials (RCT), before-and-after trials or cohort studies comparing conservative with liberal oxygen therapy in critically ill adults (aged ≥18 years) were retrieved. The main outcomes were mortality and ventilator-free days, length of stay, and adverse effects assessed by random-effects meta-analyses. We used the GRADEpro Guideline Development Tool and Trial sequential analysis (TSA) to evaluate the quality of evidence and information size, respectively. Meta-regression was conducted to explore heterogeneity among studies. Findings: Five RCTs and 2 before-and-after trials enrolled 16188 ICU patients. Compared with liberal oxygen therapy, a conservative oxygen strategy (maintaining peripheral oxygen [SpO2] ≤ 98% or arterial oxygen partial pressure [PaO2] ≤ 100 mmHg at the lowest possible FiO2) decreased hospital mortality (RR = 0.88; 95% CI, 0.81-0.95; p = 0.002, moderate quality), especially for patients receiving MV (N = 12327; RR = 0.91; 95% CI, 0.84-1.00; p = 0.05, moderate quality). Moreover, it reduced hospital length of stay (Std. MD = -0.04; 95% CI, -0.06- -0.01; p = 0.01, moderate quality) and increased ventilator-free days either at day 28 (Std. MD = 0.04; 95% CI, 0.01-0.08; p = 0.005, low quality) or during ICU stay (Std. MD = 0.49; 95% CI, 0.30-0.68; p < 0.00001, low quality). The incidence of new bacteremia was much lower in the conservative oxygen therapy group (RR = 0.53; 95% CI, 0.30-0.92; p = 0.02, very low quality). TSA indicated that no more clinical studies should be conducted to prove a beneficial effect of conservative oxygen therapy on hospital length of stay rather than ICU length of stay for critically ill patients. Interpretation: In critically ill adults, conservative oxygen therapy improves hospital mortality, decreases hospital length of stay and increases ventilator-free days, without impacting overall adverse effects. More clinical trials with better designs are needed to optimize the strategy of conservative oxygen therapy in ICU. Funding Statement: This work was supported by the National Natural Science Foundations of China (No. 81571874, 81670074, 81870066), the Key Research and Development Plan of Jiangsu Province (BE2018743), the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX17_0168), Natural Science Foundation of Jiangsu Province (BK20171271), the Jiangsu Provincial Medical Youth Talent (QNRC2016807) and Third Level Talents of the “333 High Level Talents Training Project” in the fifth phase in Jiangsu (LGY2016051). Declaration of Interests: None declared.

Protocol and statistical analysis plan for the mega randomised registry trial comparing conservative vs. liberal oxygenation targets in adults with sepsis in the intensive care unit (Mega-ROX Sepsis)

Conservative or liberal oxygen therapy for mechanically ventilated adults with acute brain pathologies: A post-hoc subgroup analysis.

BackgroundThe acknowledgment that conservative oxygen therapy (COT) was related to better prognosis in the intensive care unit (ICU) was challenged recently. We conducted an updated meta-analysis aimed to determine whether liberal oxygen therapy (LOT) or COT is associated with better improve clinical outcomes.MethodsWe systematically searched the electronic databases (PubMed, Web of Science and Embase) up to May 2021 for randomized controlled trials (RCTs). The primary outcome was the mortality of the final follow-up time and secondary outcomes were ICU mortality, the ICU length of stay and the number of ventilator-free days.ResultsA total of 7 RCTs were included, with 2166 patients admitted to the ICU. There was no significant difference in the primary outcome between the LOT and COT. Additionally, LOT could not significantly increase ICU mortality and the ICU length of stay compared with COT.ConclusionsThe present study showed that COT was not significantly superior to LOT in clinical outcomes. Therefore, additional high-quality studies with novel designs are required to further elucidate this controversy.

Conservative versus liberal oxygen therapy in relation to all-cause mortality among patients in the intensive care unit: a systematic review of randomized controlled trials with meta-analysis and trial sequential analysis

Protocol and statistical analysis plan for the mega randomised registry trial comparing conservative vs. liberal oxygenation targets in adults with nonhypoxic ischaemic acute brain injuries and conditions in the intensive care unit (Mega-ROX Brains)

Conservative versus liberal oxygen therapy for acutely ill medical patients: A systematic review and meta-analysis

Science, Medicine, and the Anesthesiologist

BackgroundIt remains unclear whether conservative oxygen therapy (COT) or liberal oxygen therapy (LOT) is more beneficial to the clinical outcomes of intensive care unit (ICU) patients. We systematically reviewed the efficacy and safety of conservative versus liberal oxygen therapy for ICU patients.MethodsWe systematically searched PubMed, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, MedRxiv, and BioRxiv for reports on randomized controlled trials (RCTs) that compared the effects of COT versus LOT on the clinical outcomes of ICU patients published in English before April 2024. The primary outcome was the mortality rate, secondary outcomes included ICU and hospital length of stay, days free from mechanical ventilation support (MVF), vasopressor-free time (VFT), and adverse events.ResultsIn all, 13 RCTs involving 10,632 patients were included in analyses. Meta-analysis showed COT did not reduce mortality at 30-day (risk ratio [RR] = 1.01, 95% confidence interval [CI] 0.94 to 1.09, I2 = 42%, P = 0.78), 90-day (RR = 1.01, 95% CI 0.95 to 1.08, I2 = 9%, P = 0.69), or longest follow-up (RR = 1.00, 95% CI 0.95 to 1.06, I2 = 22%, P = 0.95) compared to LOT in ICU patients. In subgroup analyses, no significant difference was observed between the two groups in terms of the different ICU, baseline P/F, and actual PaO2. In addition, COT did not affect ICU length of stay, hospital length of stay, or VFT, it only affected MVF days.ConclusionsCOT did not reduce all-cause mortality in ICU patients. Further RCTs are urgently needed to confirm the impact of COT strategy on specific populations.

Background Conservative oxygen therapy is a good alternative to liberal oxygen therapy, as it overcomes libral oxygen therapy induced hyperoxia and reduces its harmful and undesirable effects such as lung injury and, lung collapse, acute respiratory distress syndrome. Objective To systematically review the efficacy and safety of conservative versus liberal oxygen therapy, and to measure the caliber of trachea and main bronchi at the start and end of treatment by oxygen therapy to show if it has an effect on anteroposterior and transverse dimensions of trachea and main bronchi. Patients and Methods A prospective study was conducted on 72 subject were divided into 2 groups. 36 patients received liberal oxygen (group A), 36 patients received conservative oxygen (group B). Results In comparing the 2 groups, there was no statically significant difference between the two groups concerning hospital acquired infection but hospital acquired pneumonia was high in group A (p value &amp;lt; 0.05). Furthermore, length of hospital stay was statically significant higher in group A (p value &amp;lt; 0.001). Although arrhythmia was statically significant higher in group B (p value &amp;lt; 0.05). On other hand there was no statically difference between two groups as regarded vasopressor dose, new organ dysfunction, mechanical ventilation free days, attempts to lower use of mandatory MV mode which might indicate earlier attempts to wean patients, ARDS as a new complication, ICU mortality, hospital mortality and 30day mortality (p value &amp;gt; 0.05). Conclusion Both libral and conservative oxygen therapy have advantages and disadvantages, and we did not find a clear difference between both choices. Each of the two options is left to the physician, who decides to choose one of the two options according to his exeperience and the patient's condition.

Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis

Conservative or liberal oxygen therapy in adults after cardiac arrest: An individual-level patient data meta-analysis of randomised controlled trials

Background: Conservative oxygen therapy can prevent both hypoxemia and hyperoxemia, but the effect on the prognosis of patients admitted to the intensive care unit (ICU) remains controversial.Methods: All controlled studies comparing conservative oxygen therapy and conventional oxygen therapy in adult patients admitted to the ICU were searched. The primary outcome was mortality, and the secondary outcomes were length of ICU stay (ICU LOS), length of hospital stay (hospital LOS), length of mechanical ventilation (MV) hours, new organ failure during ICU stay, and new infections during ICU stay.Results: Nine trials with a total of 5,759 patients were pooled in our final studies. Compared with conventional oxygen therapy, conservative oxygen therapy did not reduce overall mortality (Z = 0.31, p = 0.75) or ICU LOS (Z = 0.17, p = 0.86), with firm evidence from trial sequential analysis, or hospital LOS (Z = 1.98, p = 0.05) or new infections during the ICU stay (Z = 1.45, p = 0.15). However, conservative oxygen therapy was associated with a shorter MV time (Z = 5.05, p < 0.00001), reduction of new organ failure during the ICU stay (Z = 2.15, p = 0.03) and lower risk of renal replacement therapy (RRT) (Z = 2.18, p = 0.03).Conclusion: Conservative oxygen therapy did not reduce mortality but did decrease MV time, new organ failure and risk of RRT in critically ill patients.Systematic Review Registration: identifier [CRD42020171055].