Strategies for lung- and diaphragm-protective ventilation in acute hypoxemic respiratory failure: a physiological trial

Abstract

Background: Insufficient or excessive respiratory effort during acute hypoxemic respiratory failure (AHRF) increases the risk of lung and diaphragm injury. We sought to establish whether respiratory effort can be optimized to achieve lung- and diaphragm-protective (LDP) targets (esophageal pressure swing - 3 to - 8 cm H₂O; dynamic transpulmonary driving pressure ≤ 15 cm H₂O) during AHRF.

Methods: In patients with early AHRF, spontaneous breathing was initiated as soon as passive ventilation was not deemed mandatory. Inspiratory pressure, sedation, positive end-expiratory pressure (PEEP), and sweep gas flow (in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO)) were systematically titrated to achieve LDP targets. Additionally, partial neuromuscular blockade (pNMBA) was administered in patients with refractory excessive respiratory effort.

Results: Of 30 patients enrolled, most had severe AHRF; 16 required VV-ECMO. Respiratory effort was absent in all at enrolment. After initiating spontaneous breathing, most exhibited high respiratory effort and only 6/30 met LDP targets. After titrating ventilation, sedation, and sweep gas flow, LDP targets were achieved in 20/30. LDP targets were more likely to be achieved in patients on VV-ECMO (median OR 10, 95% CrI 2, 81) and at the PEEP level associated with improved dynamic compliance (median OR 33, 95% CrI 5, 898). Administration of pNMBA to patients with refractory excessive effort was well-tolerated and effectively achieved LDP targets.

Conclusion: Respiratory effort is frequently absent under deep sedation but becomes excessive when spontaneous breathing is permitted in patients with moderate or severe AHRF. Systematically titrating ventilation and sedation can optimize respiratory effort for lung and diaphragm protection in most patients. VV-ECMO can greatly facilitate the delivery of a LDP strategy.

Trial registration: This trial was registered in Clinicaltrials.gov in August 2018 (NCT03612583).

Keywords: Diaphragm-protective ventilation; Hypoxemic respiratory failure; Lung-protective ventilation; Mechanical ventilation.

Fig. 1

Trial design. A Study procedure to test the effect of different interventions on the probability of achieving lung- and diaphragm-protective targets. B Approach to adjusting ventilation and sedation to achieve lung- and diaphragm-protective targets. The algorithm used for titration in the trial is provided in Additional file 1: Fig. S2. PEEP: positive end-expiratory pressure; VV-ECMO: veno-venous extracorporeal membrane oxygenation; LDP: lung- and diaphragm-protective; ∆Pes: esophageal pressure swing; ∆P_L,dyn: dynamic driving transpulmonary pressure

Fig. 2

Physiological outcomes after each step in the trial. The proportion of patients who met lung and diaphragm-protective (LDP) targets at the end of each study phase in those not receiving VV-ECMO (A) and those receiving VV-ECMO (B). Below the stacked bar plots, the corresponding distributions of respiratory effort (ΔPes) and lung-distending pressure (ΔP_L,dyn) are shown. Error bars represent 25^th and 75^th percentiles with median (circle). *Not all eligible patients received partial neuromuscular blockade due to decision of the attending physician. LDP: lung and diaphragm protection, VV ECMO: veno-venous extracorporeal membrane oxygenation, pNMBA: partial neuromuscular blockade, ∆Pes: esophageal pressure swing, ∆P_L,dyn: dynamic transpulmonary driving pressure

Fig. 3

Effect of modifying PEEP on respiratory effort and lung-distending pressure. There was no difference in ∆Pes, ∆P_L,dyn, or the probability of meeting lung- and diaphragm-protective targets between higher or lower PEEP levels (A, B). The effects of higher vs. lower PEEP on ΔPes and ΔP_L,dyn, varied widely between patients according to the effect of changing PEEP on dynamic lung compliance (C). The probability of meeting LDP targets at the PEEP level associated with higher dynamic lung compliance was greater in comparison to the PEEP level associated with lower dynamic lung compliance (D). Error bars represent 25^th and 75^th percentiles with median (circle). LDP: lung and diaphragm protection, ∆Pes: esophageal pressure swing, ∆P_L,dyn: dynamic transpulmonary driving pressure, C_L,dyn: dynamic lung compliance, PEEP: positive end-expiratory pressure

Fig. 4

Effect of increasing sweep gas flow on ventilation, respiratory effort, and lung-distending pressure. Error bars represent 25th and 75th percentiles with median (circle). ∆Pes: esophageal pressure swing, ∆P_L,dyn: dynamic transpulmonary driving pressure