Early individualized positive end-expiratory pressure guided by electrical impedance tomography in acute respiratory distress syndrome: a randomized controlled clinical trial

Abstract

Background: Individualized positive end-expiratory pressure (PEEP) by electrical impedance tomography (EIT) has potential interest in the optimization of ventilation distribution in acute respiratory distress syndrome (ARDS). The aim of the study was to determine whether early individualized titration of PEEP with EIT improved outcomes in patients with ARDS.

Methods: A total of 117 ARDS patients receiving mechanical ventilation were randomly assigned to EIT group (n = 61, PEEP adjusted based on ventilation distribution) or control group (n = 56, low PEEP/FiO₂ table). The primary outcome was 28-day mortality. Secondary and exploratory outcomes were ventilator-free days, length of ICU stay, incidence of pneumothorax and barotrauma, and difference in Sequential Organ Failure Assessment (SOFA) score at day 1 (ΔD1-SOFA) and day 2 (ΔD2-SOFA) compared with baseline.

Measurements and main results: There was no statistical difference in the value of PEEP between the EIT group and control group, but the combination of PEEP and FiO₂ was different between groups. In the control group, a significantly positive correlation was found between the PEEP value and the corresponding FiO₂ (r = 0.47, p < 0.00001) since a given matched table was used for PEEP settings. Diverse combinations of PEEP and FiO₂ were found in the EIT group (r = 0.05, p = 0.68). There was no significant difference in mortality rate (21% vs. 27%, EIT vs. control, p = 0.63), ICU length of stay (13.0 (7.0, 25.0) vs 10.0 (7.0, 14.8), median (25th-75th percentile); p = 0.17), and ventilator-free days at day 28 (14.0 (2.0, 23.0) vs 19.0 (0.0, 24.0), p = 0.55) between the two groups. The incidence of new barotrauma was zero. Compared with control group, significantly lower ΔD1-SOFA and ΔD2-SOFA were found in the EIT group (p < 0.001) in a post hoc comparison. Moreover, the EIT group exhibited a significant decrease of SOFA at day 2 compared with baseline (paired t-test, difference by - 1 (- 3.5, 0), p = 0.001). However, the control group did show a similar decrease (difference by 1 (- 2, 2), p = 0.131).

Conclusion: Our study showed a 6% absolute decrease in mortality in the EIT group: a statistically non-significant, but clinically non-negligible result. This result along with the showed improvement in organ function might justify further reserach to validate the beneficial effect of individualized EIT-guided PEEP setting on clinical outcomes of patients with ARDS.

Trial registration: ClinicalTrials, NCT02361398. Registered 11 February 2015-prospectively registered, https://clinicaltrials.gov/show/NCT02361398 .

Keywords: ARDS; Electrical impedance tomography; Organ function; PEEP titration.

Fig. 1

Individualized positive end-expiratory airway pressure titration using electrical impedance tomography in one patient of the EIT group. Optimal PEEP is defined the intercept point of cumulated collapse and overdistension percentage curves, providing the best compromise between collapsed and overdistended lung. If the intercept point occurred between two PEEP steps, the selected PEEP corresponded to the PEEP step toward the lowest global inhomogeneity index. For the presented example, selected PEEP is 6cmH₂O

Fig. 2

Flowchart of the enrolled patients. pts, patients

Fig. 3

Distribution of the difference values and agreement of Bland–Altman plot between PEEP_eit and PEEP_{lower table} methods in the EIT group. Out of 61 patients, 41 exhibited an absolute difference value between PEEP_eit and PEEP_{lower table} ≥ 2cmH₂O. Mean difference between the PEEP_eit and PEEP_{lower table} was − 0.1 [95% limits of agreement was from 6.4 to (− 6.6) cmH₂O]

Fig. 4

Kaplan–Meier 28-day probability of survival curve for the EIT group and the control group