Lung Recruitment Assessed by Electrical Impedance Tomography (RECRUIT): A Multicenter Study of COVID-19 Acute Respiratory Distress Syndrome

Abstract

Rationale: Defining lung recruitability is needed for safe positive end-expiratory pressure (PEEP) selection in mechanically ventilated patients. However, there is no simple bedside method including both assessment of recruitability and risks of overdistension as well as personalized PEEP titration. Objectives: To describe the range of recruitability using electrical impedance tomography (EIT), effects of PEEP on recruitability, respiratory mechanics and gas exchange, and a method to select optimal EIT-based PEEP. Methods: This is the analysis of patients with coronavirus disease (COVID-19) from an ongoing multicenter prospective physiological study including patients with moderate-severe acute respiratory distress syndrome of different causes. EIT, ventilator data, hemodynamics, and arterial blood gases were obtained during PEEP titration maneuvers. EIT-based optimal PEEP was defined as the crossing point of the overdistension and collapse curves during a decremental PEEP trial. Recruitability was defined as the amount of modifiable collapse when increasing PEEP from 6 to 24 cm H₂O (ΔCollapse_24-6). Patients were classified as low, medium, or high recruiters on the basis of tertiles of ΔCollapse_24-6. Measurements and Main Results: In 108 patients with COVID-19, recruitability varied from 0.3% to 66.9% and was unrelated to acute respiratory distress syndrome severity. Median EIT-based PEEP differed between groups: 10 versus 13.5 versus 15.5 cm H₂O for low versus medium versus high recruitability (P < 0.05). This approach assigned a different PEEP level from the highest compliance approach in 81% of patients. The protocol was well tolerated; in four patients, the PEEP level did not reach 24 cm H₂O because of hemodynamic instability. Conclusions: Recruitability varies widely among patients with COVID-19. EIT allows personalizing PEEP setting as a compromise between recruitability and overdistension. Clinical trial registered with www.clinicaltrials.gov (NCT04460859).

Keywords: acute respiratory distress syndrome; electrical impedance tomography; lung recruitability; mechanical ventilation; positive end-expiratory pressure.

Figure 1.

Study protocol with applied positive end-expiratory pressure (PEEP) steps. For further details, see the Methods section. Ventilator mode is mentioned below the x-axis. Continuous monitoring of electrical impedance tomography and airway pressure and/or flow was performed throughout the protocol. Arterial blood gas and measurements of respiratory mechanics (short 0.2- to 0.3-s end-inspiratory and end-expiratory occlusions) and hemodynamics were obtained at baseline clinical PEEP level and for PEEP steps with a duration of 5 minutes. R/I ratio was assessed during a single-breath maneuver when decreasing PEEP from 16 to 6 cm H₂O (Step 1). In Step 2, before applying the decremental PEEP trial, PEEP was increased from 6 to 24 cm H₂O (or lower if not tolerated) in small steps (10 to 15 to 20 to 24 cm H₂O) of 1–2 minutes to test the patient’s tolerance; this was done in PCV mode with a driving pressure (ΔP) of 15 cm H₂O, an inspiratory to expiratory (I:E) ratio of 1:1, yielding a maximum peak airway pressure of 39 cm H₂O that was allowed. At PEEP 24 cm H₂O in VCV mode with a Vt lowered to 5 ml/kg PBW to minimize tidal recruitment effects, a maximum plateau pressure of 40 cm H₂O was accepted (Vt values were lowered if necessary). The following safety criteria were in place to ensure the patient’s tolerance: interruption of the protocol (back to preceding PEEP value) at any time if aforementioned values could not be maintained for at least 30 seconds without a drop in blood pressure (by 15 mm Hg for systolic blood pressure) or oxygen saturation as measured by pulse oximetry (Sp_O2) <85%. If stability was obtained at the previous step, the rest of the measurements were performed starting from the last PEEP level associated with stability. The protocol was aborted (back to clinical baseline settings), and the patient was classified as failure to perform the test in case of sustained hypotension (drop in mean arterial pressure, >15 mm Hg) or sustained hypoxemia (Sp_O2 <85% for at least 1 min). PBW = predicted body weight; PCV = pressure-controlled ventilation; R/I = recruitment-to-inflation; VCV = volume-controlled ventilation.

Figure 2.

Distribution of recruitability as defined by the decrease in the collapse on electrical impedance tomography when increasing positive end-expiratory pressure from 6 cm H₂O (Step 1 of protocol) to 24 cm H₂O (ΔCollapse_24–6). Groups of low, medium, and high recruitability were made using the tertiles of ΔCollapse_24–6: low (<25.3%), medium (25.4–39.6%), and high (>39.6%) recruitability.

Figure 3.

Distribution of collapse (blue) and overdistension (orange) during the decremental positive end-expiratory pressure (PEEP) trial for the three groups of recruitability (A: low recruitability, B: medium recruitability, C: high recruitability). The dotted lines indicate the group median [interquartile range] PEEP level as per the crossing point of the collapse and overdistension curves.

Figure 4.

Regional distribution of collapse (left, panels A and C) and overdistension (right, panels B and D) for the anterior (upper graphs, panels A and B) and posterior (lower graphs, panels C and D) lung and separated for the three recruitability groups. Collapse was present mainly in the dependent lung and highest for the higher recruitable patients (per our definition). Overdistension occurred primarily in the nondependent lung, with highest values found for lower recruitable patients and already at low PEEP levels. PEEP = positive end-expiratory pressure.

Figure 5.

Comparison of the optimal positive end-expiratory pressure (PEEP) according to the crossing point of the collapse and overdistension curves (PEEP trial crossing point) and the PEEP level with the highest respiratory system compliance (PEEP trial highest Crs) obtained during the decremental PEEP trial and separated for the three recruitability groups (A: low recruitability, B: medium recruitability, C: high recruitability). Individual comparison and the median with interquartile range are provided.

Figure 6.

Distribution of tidal ventilation for the posterior dependent (orange) and anterior nondependent (blue) lung, as obtained during the decremental positive end-expiratory pressure (PEEP) trial and separated for the three recruitability groups (A: low recruitability, B: medium recruitability, C: high recruitability). The PEEP level associated with a nondependent/dependent tidal ventilation ratio closest to 1 (i.e., the PEEP level where the y-axis is 50%) did not differ between groups. At increasing levels of PEEP, more tidal ventilation to the posterior lung is observed, which is suggestive of overdistension of the anterior lung.

Figure 7.

Mechanics, hemodynamics, and gas exchange during incremental 5-minute positive end-expiratory pressure (PEEP) steps and separated per recruitability group. (A) Oxygen saturation as measured by pulse oximetry (Sp_O2) at fixed Fi_O2. (B) Pa_O2 to Fi_O2 ratio. (C) Pa_CO2. (D) Ventilatory ratio. *P < 0.05 difference from PEEP 6 cm H₂O; ^#P < 0.05 difference from PEEP 16 cm H₂O. P values are based on linear mixed-effects models with fixed effects of PEEP, group, PEEP by group interaction, and a random effect of subject; within-group comparisons of estimated means were made with the Tukey method. Interaction effects of PEEP by group interaction were as follows: Sp_O2, P < 0.001; Pa_O2/Fi_O2, P < 0.001; Pa_CO2, P < 0.001; Ventilatory ratio, P = 0.425.