High Pleural Pressure Prevents Alveolar Overdistension and Hemodynamic Collapse in Acute Respiratory Distress Syndrome with Class III Obesity. A Clinical Trial

Abstract

Rationale: Obesity is characterized by elevated pleural pressure (Ppl) and worsening atelectasis during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS).Objectives: To determine the effects of a lung recruitment maneuver (LRM) in the presence of elevated Ppl on hemodynamics, left and right ventricular pressure, and pulmonary vascular resistance. We hypothesized that elevated Ppl protects the cardiovascular system against high airway pressure and prevents lung overdistension.Methods: First, an interventional crossover trial in adult subjects with ARDS and a body mass index ≥ 35 kg/m2 (n = 21) was performed to explore the hemodynamic consequences of the LRM. Second, cardiovascular function was studied during low and high positive end-expiratory pressure (PEEP) in a model of swine with ARDS and high Ppl (n = 9) versus healthy swine with normal Ppl (n = 6).Measurements and Main Results: Subjects with ARDS and obesity (body mass index = 57 ± 12 kg/m2) after LRM required an increase in PEEP of 8 (95% confidence interval [95% CI], 7-10) cm H2O above traditional ARDS Network settings to improve lung function, oxygenation and [Formula: see text]/[Formula: see text] matching, without impairment of hemodynamics or right heart function. ARDS swine with high Ppl demonstrated unchanged transmural left ventricular pressure and systemic blood pressure after the LRM protocol. Pulmonary arterial hypertension decreased (8 [95% CI, 13-4] mm Hg), as did vascular resistance (1.5 [95% CI, 2.2-0.9] Wood units) and transmural right ventricular pressure (10 [95% CI, 15-6] mm Hg) during exhalation. LRM and PEEP decreased pulmonary vascular resistance and normalized the [Formula: see text]/[Formula: see text] ratio.Conclusions: High airway pressure is required to recruit lung atelectasis in patients with ARDS and class III obesity but causes minimal overdistension. In addition, patients with ARDS and class III obesity hemodynamically tolerate LRM with high airway pressure.Clinical trial registered with www.clinicaltrials.gov (NCT02503241).

Keywords: acute respiratory distress syndrome; hemodynamics; intrathoracic pressure; mechanical ventilation; obesity.

Figures

Figure 1.

Clinical study of patients with acute respiratory distress syndrome (ARDS) and class III obesity versus patients with ARDS without obesity. Overdistension and collapse during a similar sequence of positive end-expiratory pressure (PEEP) and regional pressure–volume (P–V) curves for the most nondependent and the most dependent regions of interest (ROIs) are shown. (A) Overdistension and (B) collapse measured by using electrical impedance tomography in patients with ARDS and class III obesity versus patients with ARDS without obesity are shown. A mixed linear model was used for overdistension (P = 0.002 for interaction) and collapse (P < 0.001 for interaction), and for similar PEEP, overdistension was higher in patients with ARDS and without obesity and collapse was higher in patients with ARDS and class III obesity. Regional P–V curves were built for the most non–gravity-dependent ROI (ROI-1) and the most dependent ROI (ROI-3) (see Figure E1). The regional variations in EELV were calculated by using electrical impedance tomography for each PEEP (see online supplement). ROI-1 are shown in (C) patients with ARDS and class III obesity and in (E) patients with ARDS without obesity. Of note, for similar PEEP values, the P–V curve shape was different: in patients with ARDS and class III obesity, it was linear, and in patients with ARDS and without obesity, it showed positive exponential growth (mixed linear model, P = 0.002 for interaction). ROI-3 are shown in (D) patients with ARDS and class III obesity and in (F) patients with ARDS without obesity. Again, for similar PEEPs, P–V curve shapes were different. In patient with ARDS and class III obesity, the curve showed exponential negative decay, whereas in patients with ARDS without obesity, it was linear (mixed linear model, P = 0.001 for interaction). Data are presented as the mean ± SD (confidence interval). EELV = end-expiratory lung volume.

Figure 2.

Clinical study. Transthoracic echocardiography in patients with acute respiratory distress syndrome (ARDS) and class III obesity. The right heart function was evaluated for each study phase: mechanical ventilation guided by the ARDS Network (LungARDSnet) and a sequence of procedures (lung recruitment maneuver → decremental positive end-expiratory pressure trial → second lung recruitment maneuver → optimal positive end-expiratory pressure) to recruit lung atelectasis (LungRECRUITED). (A) TAPSE was measured in 17 patients, and there was no significant difference between phases. (B) S′ was measured in 11 patients, and there was no significant difference between phases. (C) CVP was measure in nine patients for each study phase. Data are presented as the mean ± SD. *LungARDSnet versus LungRECRUITED: P = 0.03; mean of differences, 3; 95% confidence interval, 0.4–5.6. CVP = central venous pressure; S′ = tricuspid systolic excursion velocity; TAPSE = tricuspid annular plane systolic excursion.

Figure 3.

Clinical and swine studies. Relative V./Q. ratio per region of interest (ROI) in patients with acute respiratory distress syndrome (ARDS) and class III obesity and swine with induced ARDS and high pleural pressure. Relative V./Q. ratio in 3 ROIs (see Figure E1 for ROI selection). (A) Patients with ARDS and class III obesity (10 patients underwent the V./Q. test with electrical impedance tomography). The ROIs changed the ratio toward a more balanced matching from LungARDSnet to LungRECRUITED. *ROI-1: P = 0.0195; median of differences, −0.36; 97.85% confidence interval (CI), −1.73 to 0.02. †ROI-2: P = 0.0195; median of differences, 0.11; 97.85% CI, −0.05 to 0.26. ‡ROI-3: P = 0.0195; median of differences, 0.15; 97.85% CI, 0.03 to 0.36. (B) Swine with induced ARDS and high pleural pressure (9 swine underwent the V./Q. test with electrical impedance tomography). *ROI-3: P = 0.0056; mean of differences, 0.4; 95% CI, 0.2 to 0.7. Data are presented as the mean ± SD. LungARDSnet = mechanical ventilation guided by the ARDS Network; LungCOLLAPSED = low airway pressure to promote alveolar derecruitment; LungRECRUITED = a sequence of procedures (lung recruitment maneuver → decremental positive end-expiratory pressure trial → second lung recruitment maneuver → optimal positive end-expiratory pressure) to recruit lung atelectasis.

Figure 4.

Swine study. Effect of different numbers of transpulmonary pressure (Pl; during respiratory cycles and during an expiratory pause) on the transmural (TM) right ventricular (RV) and left ventricular (LV) pressure in one healthy swine with normal pleural pressure and in one swine with induced acute respiratory distress syndrome (ARDS) with high pleural pressure due to increased abdominal loading. (A) Healthy swine with normal pleural pressure. Pl, TM RV pressure, and TM LV pressure at low-airway-pressure ventilation with positive end-expiratory pressure (PEEP) = 7 cm H2O (LungPEEP7) and after a lung recruitment maneuver followed by PEEP = 19 cm H2O (LungPEEP19) are shown. TM RV pressure remained unaltered, and TM LV pressure showed a significant drop during the increase in Pl from LungPEEP7 to LungPEEP19 (black arrow). (B) Swine with induced ARDS with high pleural pressure due to increased abdominal loading. Pl, TM RV pressure, and TM LV pressure at LungCOLLAPSED and LungRECRUITED are shown. TM RV pressure expressively dropped (black arrow), and TM LV pressure did not change with the increase in Pl. LungCOLLAPSED = low airway pressure to promote alveolar derecruitment; LungRECRUITED = a sequence of procedures (lung recruitment maneuver → decremental PEEP trial → second lung recruitment maneuver → optimal PEEP) to recruit lung atelectasis.