In our meta-analysis, we found that conservative oxygen therapy could not decrease the rate of mortality, ICU LOS, and hospital LOS and new infection during ICU stay in critically ill patients. But conservative oxygen therapy could reduce the MV time and the new organ failure during ICU stay.
The advantages of conservative oxygen therapy could not be denied. Conventional therapy would put 44.5% of the patients exposed to hyperoxemia, which is only about 11.4% in conservative oxygen group.20 The disadvantages of hyperoxemia have been well demonstrated by many researches. First of all, high inspired oxygen concentrations would inhibit immune system: compromising the ability of macrophages,23 suppressing the production of cytokine,24 causing structural changes within alveolar macrophages and leading to serious impairment of their antimicrobial activity.25,26 Secondly, pulmonary injury would be induced by hyperoxemia As mentioned above, hyperoxemia can result in decreased mucociliary clearance, atelectasis, inflammation, pulmonary edema, and eventually interstitial fibrosis.27,28 The combination of the injury of immune system and pulmonary was related with higher risk of ventilator associated pneumonia (VAP). A retrospective observational study on 503 enrolled patients showed that both hyperoxemia at ICU admission (OR = 1.89, 95% CI 1.23 ~ 2.89, p = 0.004), and percentage of days with hyperoxemia (OR = 2.2, 95% CI 1.08 ~ 4.48, p = 0.029) were independently associated with VAP.29 As studies showed, the rate of VAP is associated with longer MV period.30 Moreover, two of enrolled studies showed a trend to lower use of mandatory MV mode in conservative oxygen group,19,21 which might indicate earlier attempts to wean patients in response to lower FiO2 requirement. This explains the significant shorter MV hours in conservative oxygen therapy group. Third, every organ not just the lung would be damaged by production of reactive oxygen species (ROS) resulted from high concentration oxygen. ROS-mediated stress can lead to cellular necrosis and apoptosis.31 In addition, oxidative stress is responsible for direct damage to biological molecules and indirect injury through the release of cytotoxic products and mutagenic effects of lipid oxidation.32 ROS-mediated stress and oxidative stress caused by high inspired oxygen concentrations would promote the systemic organ failure; otherwise the decline of ROS in the conservative oxygen therapy group would lead to less new organ failure during the ICU stay .
However, despite the advantages of conservative oxygen therapy, lower mortality, shorter ICU LOS and shorter hospital LOS were not been found in our study. We think the following reasons might explain. First of all, there were many factors contributes to the mortality of patients. Although conservative oxygen therapy could bring some benefit to patients, but other many factors such as the severity of baseline disease et al. also contributes significantly to mortality, ICU LOS and hospital LOS,33 Thus, the benefit of conservative oxygen therapy could be not strong enough to show a significant statistic significant when combined with so many factors. Secondly, conservative oxygen therapy actually puts patients in a higher risk of hypoxia at the same time when avoiding the hyperoxemia. Hypoxia was also related with higher mortality,34 which might offset the advantages of conservative oxygen therapy.
In addition, we did not found any advantages of conservative oxygen therapy in new infection during ICU stay compared with conventional oxygen therapy. As we all know, the incidence of new infection might have been underestimated because only those ascertained by microbiological samples were recorded.16 Moreover, only two of enrolled studies reported the data about new infection during ICU stay. Thus, the small sample might also be one of the reasons.
There are also several limitations in our study, which need to be addressed. First, high clinical heterogeneity existed in our analysis: 1)the primary disease of patients included in our enrolled studies was mixed, conservative oxygen therapy might have more benefit in hypoxic ischemic encephalopathy, but we could not do the subgroup analysis due to lack of data; 2) the severity of patients who admitted into ICU was also varies in included studies; 3) although all the studies divided participated into conservative and conventional groups, the actual oxygenation level in each group were varies in included studies. Second, because of the limit of FiO2 titration, there were episodes when the oxygenation level of patients was out of the range of target oxygenation level, which might influence the application of our conclusions.