Acute Respiratory Distress Syndrome (ARDS) was first described in 1967 and is characterized by the abrupt onset of clinically significant hypoxemia with the presence of diffuse pulmonary infiltrates.1 The criteria were updated in 2012 in the so-called Berlin definition of ARDS in adults based on the severity of hypoxemia represented by the ratio of the partial pressure of oxygen in arterial blood to inspired oxygen.2 ARDS is a life-threatening condition of seriously ill patients and is a prevalent cause of acute respiratory failure, carrying high mortality of 30–40%.3 The pathophysiological features were the ratio of ventilation to perfusion mismatch, decreased thoracic compliance, increased dead space, and elevated pulmonary arterial pressure. Therefore, early recognition of ARDS modifiable risk factors and the avoidance of aggravating factors during the patient's hospital stay can help decrease its development.4 Of all adjunctive therapies, lung-protective ventilation is still the key to a better outcome in ARDS. Recent guidelines on mechanical ventilation in ARDS provide evidence-based recommendations related to 6 interventions, including low tidal volume and inspiratory pressure ventilation, prone positioning, high-frequency oscillatory ventilation, higher vs. lower Positive End-Expiratory Pressure (PEEP), lung recruitment maneuvers, and extracorporeal membrane oxygenation.5

Setting PEEP appropriately is now recognized as an important aspect of a lung-protective ventilation strategy and not just a strategy to improve oxygenation. Setting PEEP levels 5 cm H2O may be harmful in the acute phase of ARDS. Setting PEEP appropriately is a balance between maintaining alveolar recruitment and avoiding alveolar over distention.6 Several methods have been proposed for PEEP titration in an individual patient with ARDS, including gas exchange, compliance, pressure-volume curve, stress index, esophageal manometry, lung volume, imaging.7 Of the imaging method, Electrical Impedance Tomography (EIT) plays an important role.

EIT is a bedside monitoring tool that non-invasively visualizes local ventilation and arguably lung perfusion distribution. EIT images possess a high temporal and functional resolution allowing the visualization of dynamic physiological and pathological changes on a breath-by-breath basis.8 Current studies focus mainly on its clinical applications to quantify lung collapse, tidal recruitment, and lung over distension to titrate PEEP, which is new in the PEEP setting.9–12

Previous studies compared the methods of conventional PEEP titration strategies but not EIT-based individual PEEP setting. Thus, to assess the effect of EIT-based individual PEEP setting, we undertook a systematic review and meta-analysis investigating the difference between two methods (EIT and other method) in the final P/F ratio or the final compliance when PEEP is titrated using those methods.

Four electronic databases (PUBMED, EMBASE, Web Of Science, and the Cochrane Library) were searched from inception to December 2020, for trials investigating any other PEEP titration strategies and EIT based individual PEEP setting of ARDS patients, with MeSH headings and text words (discussed in detail in search strategies, web appendix). We searched for any additional studies in the references of all identified publications, including previous relevant meta-analyses and narrative reviews. This study is registered with the INPLASY website, number INPLASY202160094.

Our study indicates that ARDS patients who have optimized PEEP with Electrical Impedance Tomography have a significantly higher PaO2/FiO2-ratio than those titrated with the conventional type. However, the respiratory system compliance was similar in the two groups. PEEP was not significantly decreased in the EIT group compared with the conventional group indicating that EIT-drived PEEP has similar efficacy to conventional strategies.

Raised compliance compared to subgroups and raised PaO2/FiO2-ratio in the EIT group was maintained across important subgroups associated with patient demographics, the severity of hypoxemia, patient position, imaging feature, tidal volume, other clinician therapies, and use of prophylactic measures. This observation suggests that our findings reflect a true effect of Electrical Impedance Tomography, rather than an artifact of statistical heterogeneity or specific patient or procedural characteristics. Notably, noninvasive and visible are the specific feature of EIT. Despite this difference, the conventional strategies are maintained, suggesting that the effect of dynamic imaging design does not take place of that of conventional strategies in treatment guidance.

In the recent decade, Electrical Impedance Tomography (EIT) is becoming emerging as an easily accessible imaging radiation-free techniques that allow continuous and functional respiratory monitoring at the bedside, based on the repeated measurement of the surface voltages resulting from a rotating injection of high frequency and low-intensity alternating current that circulates between the electrodes located around the chest. The electrodes collect the information on impedance by forming a relative image concerning a reference. The tissues allow the passage of current with little resistance, however, with gas the opposite occurs. In this way, it is possible to perform plethysmography of the volume entering upon each inspiration and in each region of interest.13 Previous studies mainly focus on randomized controlled trials of ventilation strategies and monitoring, animal models on cardio-pulmonary perfusion, and reviews of clinical practice,8,9,13–21 but without a meta-analysis of EIT-drived PEEP titration for ARDS patients yet. No meta-analysis of EIT presents up to December 2020, probably because of EIT coming out not long and being not widely used. Thus we performed this meta-analysis investigating the use of EIT-drived PEEP titration for the management of patients with ARDS and establish evidence. The previous meta-analysis reported a lot of conventional PEEP settings (including Gas exchange, compliance, pressure-volume curve, stress index, esophageal manometry, lung volume, Imaging) for patients with ARDS, of which mostly compared the effect of high PEEP level and low PEEP level on outcomes.22–31 Our findings stand in clear distinction from those of past studies that did not reach a consensus on this topic. A previous meta-analysis22–26 had limitations and focused on the conventional and indisputable PEEP setting, whereas our study is broad in its scope with robust analyses done by a multidisciplinary team.

However, our study is not without limitations. First, only eight studies were included, all of which are small-sample trials, resulting in poor test efficiency. At the same time, all trials did not report the allocation concealment scheme, which may have selection bias. Only two of the studies were RCT. Six studies did not report their blinded implementation schemes, and the measurement biases might exist. These defects will affect the internal and external authenticity of the results.

In conclusion, we found that EIT-guided PEEP titration was associated with a raise respiratory system compliance and significant raise in PaO2/FiO2-ratio, and had similar efficacy to their conventional counterparts. Our findings suggest that the EIT group retains a favorable balance between safety and efficacy when compared with the conventional type. These results provide clinicians and health-care policymakers with a comprehensive assessment and high-quality evidence on the safety and efficacy of atraumatic needles as a superior option for patients with ARDS.

This research received grant from health special talents program of Suzhou high tech Zone. The authors report no conflicts of interest.

Mengnan Yu: Conceptualization, Formal analysis, Investigation, Project administration, Validation, Visualization, Writing – original draft, Writing – review & editing. Yanjun Deng: Conceptualization, Investigation, Project administration, Validation, Writing – original draft, Writing – review & editing. Jun Cha: Data curation. Lingyan Jiang: Data curation, Formal analysis, Validation, Visualization. Mingdeng Wang: Data curation, Supervision. Shigang Qiao: Data curation, Formal analysis, Investigation, Supervision. Chen Wang: Conceptualization, Investigation, Project administration, Supervision, Visualization, Writing – review & editing.